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Professor Jennifer Littlechild

Professor of Biological Chemistry

3468

723468

Biocatalysis Centre BC2.1

Biocatalysis Centre, University of Exeter, The Henry Wellcome Building for Biocatalysis, Stocker Road, Exeter, EX4 4QD , UK

Professor Jenny Littlechild and postdoctoral researcher Dr Kirsty Line. Photo copyright Tim Pestridge

Overview

I am a biochemist/structural biologist with interests in the structure and mechanism of a range of microbial and human enzymes. I have special interest in industrial biotechnology and biocatalysis. Current research studies involve the structural and mechanistic characterisation of the C-C bond forming enzymes transketolase and aldolase, carbonic anhydrases, vanadium haloperoxidases, Baeyer-Villiger monooxygenases, aminoacylases, novel esterases and lipases, expoxide hydrolases, gamma lactamases, alcohol dehydrogenases, dehalogenases, transaminases,cellulases and other enzymes from thermophilic bacteria and archaea. Many of these enzymes are used in combination with conventional chemical synthesis for the production of new high value optically pure drugs of interest to pharmaceutical companies. Other enzymes have applications within the healthcare industries and in different areas of industrial biotechnology.

Qualifications

1973 PhD Biophysics, Kings College, University of London
1969 MI Biology (by examination) Biochemistry, special topic Microbial Biochemistry
1967 LI Biology (by examination) Physical and Organic Chemistry, Biochemistry

Career

1999-present Professor of Biological Chemistry, University of Exeter Head of Biocatalysis within the Bioeconomy Centre.
1991-1994 Senior Lectureship (Wellcome Trust) in Biological & Medicinal Chemistry, University of Exeter
1984-1991 SERC Senior Research Fellow, Biotechnology Directorate, University of Bristol
1981-1984 Principal Investigator, MRC Project Grant, Department of Biochemistry, University of Bristol
1975-1981 Group Leader, Max-Planck Institute fur Molekular Genetik, Berlin, Germany
1974-1975 Postdoctoral Fellow, Department of Biochemical Sciences, Princeton University, USA
1974 Department of Biochemical Sciences, Princeton University, USA
1973 Department of Biophysics, Kings College, University of London

Research group links

Cellular and Chemical Biology

Professor Jenny Littlechild with a member of her research group

Research

Research interests

Our work is multi-disciplinary in nature covering molecular genetics (site-directed mutagenesis and gene isolation and cloning), protein purification and characterisation, and structural analysis by NMR, X-ray crystallography and molecular modelling.

Biotransformations. Structural and mechanistic characterisation of the C-C bond forming enzymes transketolase and aldolase, vanadium haloperoxidases, Baeyer-Villiger monooxygenases, aminoacylases, novel esterases and lipases, gamma lactamases, alcohol dehydrogenases, nitrilases, transaminases, dehalogenases,expoxide hydrolases, lactonases,cellulases and other enzymes from thermophilic bacteria and archaea have been carried out. The results have provided information on the properties, substrate specificity and structure of these industrially important biocatalysts. This work has attracted industrial collaborations with a number of international companies and SME's including Chirotech/DowPharma, Stylacats, Affiniti/Biomol, TMO Biotech, Alphamerix, PML Corporation Ltd., Fluka/Sigma Aldrich, DSM, YorkPharma, Diversa and Glaxo-Smith Kline,Unilever and Evonik. I have co-ordinated grants with DTI and Innovate, UK and have been involved in EU grants within framework 4,6 and 7 and ERA-net and ERA-CoBiotech in 2017. I am Vice-Chair and UK representative of the European Section on Applied Biocatalysis and an affiliated member of the CoE in Biocatalysis in Manchester.

Human enzymes and their importance in drug design. The structures of several human glycolytic enzymes have assumed special significance due to their potential use in drug design. My research has concentrated on phosphoglycerate kinase and aldolase and our studies have contributed to the determination, three dimensional structure and mechanism of these enzymes. Other human enzymes with medicinal interest have recently been studied such as human glucokinase (diabetes) and perioxiredoxin and sulfiredoxin (antioxidant proteins and their complexes with Peninsula Medical School) and pyroglutamyl carboxypeptidase (peptide N-terminal modification).

Other collaborations with Prof Brophy, Aberystwyth on the structural investigation of nematode specific GST proteins. Structural studies on novel plant enzymes from the vitamin C pathway and involved in fungal infection with Exeter colleagues. Russian Academy of Sciences for thermophilic transfer enzymes and thermophilic cell factories, Prof Nils Birkeland,Bergen, Norway and Prof Peter Schoeheit, University of Keil, thermophilic transfer enzymes, Dr Daniela Monti, ICRM, Milan, Italy for thermophilic transfer enzymes. Prof Siebers, Essen, Germany for extremolyte production in thermophilic bacteria and archaea.

Research projects

Novel extremophilic enzymes for new applications in Healthcare Products

BBSRC Training Grant, Industrial CASE with Unilever 2021-2025.

Development of Novel Robust Laundry Enzymes for Cold Wash Applications by both rational and directed evolution and using micro-fluidic approaches

BBSRC Training Grant, Industrial CASE with Unilever 2020-2024

Novel extremophilic hydrolytic enzymes for consumer product applications including improved extremophilic enzyme expression platform development

BBSRC Training Grant, Industrial CASE with Unilever 2018-2022

Molecular Mechanics of Enzymes

EPSRC, Physics of Life Grant with Prof Frank Vollmer Joint PI, CoPIs Prof Neil Gow and Prof Peter Winlove 2019-2022

EU Horizon 2020 Large Consortium Grant RADICALZ - Rapid discovery and development of enzymes for novel and greener consumer products with Dr Fabrice Gielen, LSI Exeter and partners at University of Madrid, Spain, University of Greifswald, Germany, University of Zagreb, Croatia, Polytechnique of Lausanne, Switzerland, Institut National Applied Sciences, Toulouse, France, Industries, Brain, Germany. Hanson, Denmark and 4 SMEs 2021-2025

ERA-Net Co-fund on Food Systems and Climate (FOSC) THERMOK with University of Bergen, CEA Research Unit, France, Free State University, South Africa, University of Nairobi, Kenya, Norwegian Research Centre, Norway DEFRA Funded UK 2021-2024

ERA-CoBiotech HOTSOLUTE -- Thermophilic bacteria and archaeal chassis for extremolyte production

March 2018 to April 2021 BBSRC with University of Essen, Germany, National Academy of Sciences, Russia, ICRM Institute, Milan, Italy, University of Stellenbosch, South Africa (Fairdom Data Management), sub-contractor and Evonik and SME in Germany

TIPS-Thermophilic Isomerases for Industrial Applications ERA-IB Grant March 2018-Feb 2019

Funding from Norway Research Council and CSIC, Spain Part of ERA-IB grant sub-contractor with CSIC, Spain, University of Bergen, Norway, University of Kiel, Germany and Sigma-Aldrich, Merck as advisors.

Synergy of Novel Chemistry and Novel Biology to Combat unmet cleaning needs

Innovate UK November with Unilever Nov 2018 to Sep 2020

In collaboration with SME Protein Technologies, UK, University of Liverpool

Intervention on Enzyme Stability – Unilever

Oct 2013 –Sep 2017

Novel enzyme diversity for improving cleaning and hygiene Innovation UK Catalyst with Unilever

Sep 2016-Aug 2017.

Exploration of Novel Host Organisms as Cell Factories
Industrial studentship Glaxo Smith Kline
Oct 2012 – Sep 2016

THERMOGENE ERA-inet Industrial Biotechnology
With SME in Russia Moltech and partners in Norway and Germany
BBSRC funded in UK
March 2013- Feb 2016

EU Large Consortium Grant ‘Hotzyme’ Biocatalysis Centre
International Companies – Sigma Aldrich and Novozymes, SMEs and academic partners,
1st April 2011-31st March 2015

Unilever GrantEnzyme Stabilisation – Intervention Routes Industrial grant
Dec 2011-Nov 2012
Extension for Dec 2012
Extension Jan 2013 – Dec 2013

Statoil Industrial Grant –Investigating Kinetics of Enzymes in Microreactors
Jan 2012 – Dec 2012

Succinate Dehydrogenase as a target for anti-microbial and anti-fungal fluorinated compounds
iNET Award with local company Darr House (SME) with Dr Steven Bates
May 1st 2011

KTN SPARK Award with Gwent Group, UK (SME)
Identification, Expression, Purification and Analysis of Novel Thermophilic Alcohol Oxidases
(Funding from Tech. Strategy Board, EU, Defra and BBSRC)
Feb 14th 2011 – August 13th 2011

Characteristion of novel enzymes from the marine algal virus EhV-86 and evaluation of their use for commercial biocatalysis
BBSRC Studentship CASE partner PML Cooperation Ltd
10-2007 - 09-2011

Novel Halogenating and Dehalogenase enzymes from marine microbes
BBSRC Studentship CASE partner Aquapharm
10-2007 - 09-2011

Starch Degrading Enzymes
Industrial Project Diversa, USA ,

Dehydrogenases of Importance in Drug Development
Industrial Project York Pharma, UK
2005 - 2007

Commercial exploitation of Marine Enzymes
DTI Fasttrack with Aquapharm, Oban
12-2006 - 11-2008

Baeyer-Villiger Enzymes and Application in Biotransformations
BBSRC
12-2005 - 1-2008

High Throughput Biocatalytic Synthesis and Screening in Micro Reactors
EPSRC
07-2005 - 06-2008

Effective and Substainable Control Strategies for Liver Fluke in Europe
EU Framework 6
005 - 2008

Research networks

South West Structural Biology Consortium, UK
Collaborations with UCL London, Prof. J. Ward, Biochemistry and Dr Paul Dalby and Prof. John Woodley, Biochemical Engineering, University of Copenhagen
EU Network on Baeyer-Villiger Monooxygenases. DSM, Germany, Fluka, Switzerland, Academic partners in France, Holland and Italy
EU Network on Thermophilic hydrolase enzymes, Hotzyme with Sigma-Aldrich, Novozymes and SMEs, University of Copenhagen Denmark, University of Essen, Germany, Montana State University, USA,Wageningen University, Netherlands,ICRM, Milan, Italy, National Hellenic research foundation, Greece, EuCRF, Israel.
ERA-IB Network on Thermophilic Transferase enzymes with Russian Academy of Sciences, University of Bergen, Norway, University , University of Keil, Germany and SME Moltech.
COST Action Cascat
COST Action Systems Biocatalysis
RedCat network, Saarbrucken University, Germany
Japan Partnership Award, BBSRC with Prof. Izumi, Prof. Oshima, Japan
Pro-Bio Faraday grouping, UK
Knowledge Transfer Network in Marine Biotechnology
INSTRUCT European Structural Biology Network
European Society of Applied Biocatalysis - Vice Chair

Research grants

2006 PML Corporation
Plymouth consultancy
2006 Diversa, USA.
Starch Degrading Enzymes
2006 DTI
Commercial exploitation of Marine Enzymes
2005 BBSRC
Baeyer-Villiger Enzymes and Application in Biotransformations
2005 EPSRC
High Throughput Biocatalytic Synthesis and Screening in Micro Reactors
2005 EU Framework 6
Design of Effective and Substainable Control Strategies for Liver Fluke in Euorpe
2004 BBSRC
Structural Studies of Enzymes Important in Biocatalysis and Drug Design REI Equipment Initiative
2004 Alphamerix/Alpha Alchemy, Cambridge/Pro-Bio Faraday
The application of thermostable alcohol dehydrogenases and lipases to medicinal biocatalysis
2004 Chirotech/Dow Pharma, Cambridge.
Optimisation of the use of thermophilic alcohol dehydrogenase enzymes for the synthesis of novel chiral alcohols of interest to pharmaceutical industry
2003 TMO Renewables UK
Dehalogenase Enzymes.
2003 Exeter,UK
Acetylation of transcription factors in relation to Oxidative Stress Affiniti/Biomol
2002 BBSRC
The Exploitation of Vanadium Haloperoxidase Enzymes in Applied Biocatalysis
2002 BBSRC Japan Partnership Award.
Development of Novel Thermostable Biocatalysts
2002 Diabetes, UK.
Glucokinase-Structure and Function Relationships to Normal and Diabetic Forms
2002 EPSRC Pro-Bio Faraday Industrial Studnetship/Stylacats, Live
Thermophilic Nitrilase Enzymes
2002 Applied Genomics Centre ESRC
10% Time commitment.
2002 BRA
Oxidative stress/Rheumatics
2002 Chirotech/Dow Pharma, Cambridge.
Human pyroglutamyl carboxypeptidase and inhibitor development
2001 BBSRC
Structural Studies on two Gamma Lactamase Enzymes with Opposite Stereospecificity
2001 Torbay Hospital Devon.
Non-Enzymically induced amino acid racemization in human proteins � a possible contributory factor in metabolic dysfunction and complications of diabetes mellitus
2000 Glaxo-Wellcome.
The bromoperoxidase from marine algae Corallina officinalis
2000 Chirotech/Dow Pharma, Cambridge.
Thermostable ADH enzymes from the archaea Sulpholobus and Pyrococcus species:applications in chiral drug synthesis
2000 Chirotech/Dow Pharma, Cambridge.
Characterisation of lactamase (amidohydrolase) enzymes of commercial value for chiral drug synthesis.
2000 Chirotech/Dow Pharma, Cambridge.
Thermostable archaeal esterase enzyme and its application for chiral drug synthesis.

Publications

Key publications | Publications by category | Publications by year

Key publications

Fraser CS, Rubio-Cabezas O, Littlechild JA, Ellard S, Hattersley AT, Flanagan SE (2012). Amino acid properties may be useful in predicting clinical outcome in patients with Kir6.2 neonatal diabetes. Eur J Endocrinol, 167(3), 417-421. Abstract. Author URL.

Sayer C, Bommer M, Isupov M, Ward J, Littlechild J (2012). Crystal structure and substrate specificity of the thermophilic serine:pyruvate aminotransferase from Sulfolobus solfataricus. Acta Crystallographica Section D: Biological Crystallography, 68(7), 763-772. Abstract.

Hickey AM, Ngamsom B, Wiles C, Greenway GM, Watts P, Littlechild JA (2009). A microreactor for the study of biotransformations by a cross-linked gamma-lactamase enzyme. Biotechnol J, 4(4), 510-516. Abstract. Author URL.

Willies SC, Isupov MN, Garman EF, Littlechild JA (2009). The binding of haem and zinc in the 1.9 a X-ray structure of Escherichia coli bacterioferritin. J Biol Inorg Chem, 14(2), 201-207. Abstract. Author URL.

Littlechild J, Garcia Rodriguez E, Isupov M (2009). Vanadium containing bromoperoxidase--insights into the enzymatic mechanism using X-ray crystallography. J Inorg Biochem, 103(4), 617-621. Abstract. Author URL.

Line K, Isupov MN, Garcia-Rodriguez E, Maggioli G, Parra F, Littlechild JA (2008). The Fasciola hepatica thioredoxin: High resolution structure reveals two oxidation states. Mol Biochem Parasitol, 161(1), 44-48. Abstract. Author URL.

Publications by category

Books

Satyanarayana T, Littlechild J, Kawarabayasi Y (2013). Preface.

Journal articles

Littlechild JA (In Press). Improving the ‘Tool Box’ for Robust Industrial Enzymes. Journal of Industrial Microbiology & Biotechnology

Alcántara AR, Domínguez de María P, Littlechild JA, Schürmann M, Sheldon RA, Wohlgemuth R (2022). Biocatalysis as Key to Sustainable Industrial Chemistry. ChemSusChem, 15(9). Abstract. Author URL.

Wohlgemuth R, Littlechild J (2022). Complexity reduction and opportunities in the design, integration and intensification of biocatalytic processes for metabolite synthesis. Frontiers in Bioengineering and Biotechnology, 10 Abstract.

Wohlgemuth R, Littlechild J, Kim B-G (2022). Editorial: Systems biocatalysis for bioprocess design. Frontiers in Bioengineering and Biotechnology, 10

Alcántara AR, de María PD, Littlechild JA, Schürmann M, Sheldon RA, Wohlgemuth R (2022). Front Cover: Biocatalysis as Key to Sustainable Industrial Chemistry (ChemSusChem 9/2022). ChemSusChem, 15(9).

Alcántara AR, Domínguez de María P, Littlechild JA, Schürmann M, Sheldon RA, Wohlgemuth R (2022). Preface to Special Issue on Biocatalysis as Key to Sustainable Industrial Chemistry. ChemSusChem, 15(9). Abstract. Author URL.

Sutter J-M, Mitchell DE, Schmidt M, Isupov MN, Littlechild JA, Schönheit P (2022). Substrate specificity of branched chain amino acid aminotransferases: the substitution of glycine to serine in the active site determines the substrate specificity for α-ketoglutarate. Frontiers in Catalysis, 2

De Rose SA, Kuprat T, Isupov MN, Reinhardt A, Schönheit P, Littlechild JA (2021). Biochemical and Structural Characterisation of a Novel D-Lyxose Isomerase from the Hyperthermophilic Archaeon Thermofilum sp. Frontiers in Bioengineering and Biotechnology, 9 Abstract.

De Rose SA, Finnigan W, Harmer NJ, Littlechild JA, consortium TH, Bettina S, Christopher B, Christina S, Benjamin M, N. IM, et al (2021). Production of the Extremolyte Cyclic 2,3-Diphosphoglycerate Using Thermus thermophilus as a Whole-Cell Factory. Frontiers in Catalysis, 1

Nepogodiev D, Simoes JFF, Li E, Glasbey J, Picciochi M, Kamarajah SK, Gujjuri R, Bhangu A, Maryam A, Azab MA, et al (2021). SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study. British Journal of Surgery, 108(9), 1056-1063. Abstract.

Zhu C, Chen Y, Isupov MN, Littlechild JA, Sun L, Liu X, Wang Q, Gong H, Dong P, Zhang N, et al (2021). Structural Insights into a Novel Esterase from the East Pacific Rise and its Improved Thermostability by a Semirational Design. Journal of Agricultural and Food Chemistry, 69(3), 1079-1090.

James P, Isupov MN, De Rose SA, Sayer C, Cole IS, Littlechild JA (2020). A ‘Split-Gene’ Transketolase from the Hyper-Thermophilic Bacterium Carboxydothermus hydrogenoformans: Structure and Biochemical Characterization. Frontiers in Microbiology, 11

K. Hussain K, Malavia D, M. Johnson E, Littlechild J, Winlove CP, Vollmer F, Gow NAR (2020). Biosensors and Diagnostics for Fungal Detection. Journal of Fungi, 6(4), 349-349. Abstract.

Yilmazer B, Isupov MN, De Rose SA, Bulut H, Benninghoff JC, Binay B, Littlechild JA (2020). Structural insights into the NAD+-dependent formate dehydrogenase mechanism revealed from the NADH complex and the formate NAD+ ternary complex of the Chaetomium thermophilum enzyme. Journal of Structural Biology, 212(3), 107657-107657.

Wang Q, Jiang M, Isupov MN, Chen Y, Littlechild JA, Sun L, Wu X, Wang Q, Yang W, Chen L, et al (2020). The crystal structure of Arabidopsis BON1 provides insights into the copine protein family. Plant J, 103(3), 1215-1232. Abstract. Author URL.

Cutlan R, De Rose S, Isupov MN, Littlechild JA, Harmer NJ (2020). Using enzyme cascades in biocatalysis: Highlight on transaminases and carboxylic acid reductases. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1868(2), 140322-140322.

Finnigan W, Cutlan R, Snajdrova R, Adams J, Littlechild J, Harmer NJ (2019). Engineering a Seven Enzyme Biotransformation using Mathematical Modelling and Characterized Enzyme Parts. ChemCatChem

Jiang M, Sun L, Isupov MN, Littlechild JA, Wu X, Wang Q, Wang Q, Yang W, Wu Y (2019). Structural basis for the Target DNA recognition and binding by the MYB domain of phosphate starvation response 1. FEBS J, 286(14), 2809-2821. Abstract. Author URL.

Isupov MN, James P, Littlechild JA (2019). Thermostable Branched-Chain Amino Acid Transaminases from the Archaea Geoglobus acetivorans and Archaeoglobus fulgidus: Biochemical and Structural Characterization. Front. Bioeng. Biotechnol, 7, 7-7.

Isupov MN, Boyko KM, Sutter J-M, James P, Sayer C, Schmidt M, Schonheit P, Nikolaeva AY, Stekhanova TN, Mardanov AV, et al (2019). Thermostable Branched-Chain Amino Acid Transaminases from the Archaea Geoglobus acetivorans and Archaeoglobus fulgidus: Biochemical and Structural Characterization (vol 7, 7, 2019). FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, 7 Author URL.

Line K, Isupov MN, LaCourse EJ, Cutress DJ, Morphew RM, Brophy PM, Littlechild JA (2019). X-ray structure of Fasciola hepatica Sigma class glutathione transferase 1 reveals a disulfide bond to support stability in gastro-intestinal environment. Scientific Reports, 9(1). Abstract.

Knight AR, Taylor EL, Lukaszewski R, Winyard PG (2018). A high-sensitivity electrochemiluminescence-based ELISA for the measurement of the oxidative stress biomarker, 3-nitrotyrosine, in human blood serum and cells. Free Radical Biology and Medicine

Wohlgemuth R, Littlechild J, Monti D, Schnorr K, van Rossum T, Siebers B, Menzel P, Kublanov IV, Rike AG, Skretas G, et al (2018). Discovering novel hydrolases from hot environments. Biotechnol Adv, 36(8), 2077-2100. Abstract. Author URL.

Ferrandi EE, Sayer C, De Rose SA, Guazzelli E, Marchesi C, Saneei V, Isupov MN, Littlechild JA, Monti D (2018). New thermophilic α/β class epoxide hydrolases found in metagenomes from hot environments. Frontiers in Bioengineering and Biotechnology, 6(OCT). Abstract.

Petrova TE, Boyko KM, Nikolaeva AY, Stekhanova TN, Gruzdev EV, Mardanov AV, Stroilov VS, Littlechild JA, Popov VO, Bezsudnova EY, et al (2018). Structural characterization of geranylgeranyl pyrophosphate synthase GACE1337 from the hyperthermophilic archaeon Geoglobus acetivorans. Extremophiles, 22(6), 877-888. Abstract. Author URL.

Isupov MN, Schröder E, Gibson RP, Beecher J, Donadio G, Saneei V, Dcunha SA, McGhie EJ, Sayer C, Davenport CF, et al (2018). The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase. Corrigendum. Acta Crystallogr D Struct Biol, 74(Pt 4). Abstract. Author URL.

Littlechild JA, Isupov MN (2017). Comments to Article by Willetts A. et al. Microorganisms 2016, 4, 38. Microorganisms, 5(3). Abstract. Author URL.

Antranikian G, Suleiman M, Schäfers C, Adams MWW, Bartolucci S, Blamey JM, Birkeland N-K, Bonch-Osmolovskaya E, da Costa MS, Cowan D, et al (2017). Diversity of bacteria and archaea from two shallow marine hydrothermal vents from Vulcano Island. Extremophiles, 21(4), 733-742. Abstract. Author URL.

de Rose SA, Novak H, Dowd A, Singh S, Lang DA, Littlechild J (2017). Stabilization of a lipolytic enzyme for commercial application. Catalysts, 7(3). Abstract.

Finnigan W, Thomas A, Cromar H, Gough B, Snajdrova R, Adams JP, Littlechild JA, Harmer NJ (2016). Characterization of carboxylic acid reductases as enzymes in the toolbox for synthetic chemistry. ChemCatChem, in press

Zarafeta D, Kissas D, Sayer C, Gudbergsdottir SR, Ladoukakis E, Isupov MN, Chatziioannou A, Peng X, Littlechild JA, Skretas G, et al (2016). Discovery and Characterization of a Thermostable and Highly Halotolerant GH5 Cellulase from an Icelandic Hot Spring Isolate. PLoS One, 11(1). Abstract. Author URL.

sayer C, Finnigan W, Isupov MN, Levisson M, Kengen SWM, van der Oost J, Harmer NJ, Littlechild JA (2016). Structural and biochemical characterisation of Archaeoglobus fulgidus esterase reveals a bound CoA molecule in the vicinity of the active site. Scientific Reports, 6, 25542-25542. Abstract.

Littlechild JA (2015). Archaeal Enzymes and Applications in Industrial Biocatalysts. Archaea, 2015, 1-10. Abstract.

Ferrandi EE, Sayer C, Isupov MN, Annovazzi C, Marchesi C, Iacobone G, Peng X, Bonch-Osmolovskaya E, Wohlgemuth R, Littlechild JA, et al (2015). Discovery and characterization of thermophilic limonene-1,2-epoxide hydrolases from hot spring metagenomic libraries. FEBS J, 282(15), 2879-2894. Abstract. Author URL.

Littlechild JA (2015). Enzymes from Extreme Environments and Their Industrial Applications. Front Bioeng Biotechnol, 3 Abstract. Author URL.

Sayer C, Isupov MN, Bonch-Osmolovskaya E, Littlechild JA (2015). Structural studies of a thermophilic esterase from a new Planctomycetes species, Thermogutta terrifontis. FEBS J, 282(15), 2846-2857. Abstract. Author URL.

Sayer C, Szabo Z, Isupov MN, Ingham C, Littlechild JA (2015). The Structure of a Novel Thermophilic Esterase from the Planctomycetes Species, Thermogutta terrifontis Reveals an Open Active Site Due to a Minimal 'Cap' Domain. Front Microbiol, 6 Abstract. Author URL.

Isupov MN, Schröder E, Gibson RP, Beecher J, Donadio G, Saneei V, Dcunha SA, McGhie EJ, Sayer C, Davenport CF, et al (2015). The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase. Acta Crystallogr D Biol Crystallogr, 71(Pt 11), 2344-2353. Abstract. Author URL.

Novak HR, Sayer C, Isupov MN, Gotz D, Spragg AM, Littlechild JA (2014). Biochemical and structural characterisation of a haloalkane dehalogenase from a marine Rhodobacteraceae. FEBS Lett, 588(9), 1616-1622. Abstract. Author URL.

Kallnik V, Bunescu A, Sayer C, Bräsen C, Wohlgemuth R, Littlechild J, Siebers B (2014). Characterization of a phosphotriesterase-like lactonase from the hyperthermoacidophilic crenarchaeon Vulcanisaeta moutnovskia. J Biotechnol, 190, 11-17. Abstract. Author URL.

Vivoli M, Novak HR, Littlechild JA, Harmer NJ (2014). Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry. Journal of Visualized Experiments(91).

Vivoli M, Novak HR, Littlechild JA, Harmer NJ (2014). Determination of protein-ligand interactions using differential scanning fluorimetry. J Vis Exp(91). Abstract. Author URL.

Littlechild J, Sayer C, Isupov M, Ward J, Littlechild J (2014). Structural studies on transaminase enzymes and applications in biocatalysis. NEW BIOTECHNOLOGY, 31, S19-S19. Author URL.

James P, Isupov MN, Sayer C, Saneei V, Berg S, Lioliou M, Kotlar HK, Littlechild JA (2014). The structure of a tetrameric α-carbonic anhydrase from Thermovibrio ammonificans reveals a core formed around intermolecular disulfides that contribute to its thermostability. Acta Crystallogr D Biol Crystallogr, 70(Pt 10), 2607-2618. Abstract. Author URL.

Sayer C, Martinez-Torres RJ, Richter N, Isupov MN, Hailes HC, Littlechild JA, Ward JM (2014). The substrate specificity, enantioselectivity and structure of the (R)-selective amine : pyruvate transaminase from Nectria haematococca. FEBS J, 281(9), 2240-2253. Abstract. Author URL.

Holley JE, Slonka J, Littlechild J, Gutowski NJ (2013). An investigation into the presence of pyroglutamyl peptidases in the Alzheimer's disease brain: relevance to pathology?. JOURNAL OF NEUROLOGY, 260, S167-S167. Author URL.

Novak HR, Sayer C, Panning J, Littlechild JA (2013). Characterisation of an L-haloacid dehalogenase from the marine psychrophile Psychromonas ingrahamii with potential industrial application. Mar Biotechnol (NY), 15(6), 695-705. Abstract. Author URL.

Novak HR, Sayer C, Panning J, Littlechild JA (2013). Characterisation of an l-Haloacid Dehalogenase from the Marine Psychrophile Psychromonas ingrahamii with Potential Industrial Application. Marine Biotechnology, 15(6), 695-705. Abstract.

Hill A, Littlechild J (2013). ChemInform Abstract: Oxidation. Haloperoxidases. ChemInform, 44(25), no-no.

Reid EL, Weynberg KD, Love J, Isupov MN, Littlechild JA, Wilson WH, Kelly SL, Lamb DC, Allen MJ (2013). Functional and structural characterisation of a viral cytochrome b5. FEBS Lett, 587(22), 3633-3639. Abstract. Author URL.

Novak HR, Sayer C, Isupov MN, Paszkiewicz K, Gotz D, Spragg AM, Littlechild JA (2013). Marine Rhodobacteraceae L-haloacid dehalogenase contains a novel His/Glu dyad that could activate the catalytic water. FEBS J, 280(7), 1664-1680. Abstract. Author URL.

Novak H, Littlechild J (2013). Marine enzymes with applications for biosynthesis of fine chemicals. , 89-106. Abstract.

Littlechild JA (2013). Protein structure and function. , 57-79. Abstract.

Sayer C, Isupov MN, Westlake A, Littlechild JA (2013). Structural studies of Pseudomonas and Chromobacterium ω-aminotransferases provide insights into their differing substrate specificity. Acta Crystallogr D Biol Crystallogr, 69(Pt 4), 564-576. Abstract. Author URL.

Hill A, Littlechild J (2012). 7.15 Oxidation: Haloperoxidases. , 7, 329-349. Abstract.

Szabo-Taylor KE, Eggleton P, Turner CAL, Lo Faro ML, Tarr JM, Toth S, Whiteman M, Haigh RC, Littlechild JA, Winyard PG, et al (2012). Lymphocytes from rheumatoid arthritis patients have elevated levels of intracellular peroxiredoxin 2, and a greater frequency of cells with exofacial peroxiredoxin 2, compared with healthy human lymphocytes. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 44(8), 1223-1231. Author URL.

Reid EL, Worthy CA, Probert I, Ali ST, Love J, Napier J, Littlechild JA, Somerfield PJ, Allen MJ (2011). Coccolithophores: functional biodiversity, enzymes and bioprospecting. Mar Drugs, 9(4), 586-602. Abstract. Author URL.

Littlechild JA (2011). Thermophilic archaeal enzymes and applications in biocatalysis. Biochem Soc Trans, 39(1), 155-158. Abstract. Author URL.

Wilson RA, Gibson RP, Quispe CF, Littlechild JA, Talbot NJ (2010). An NADPH-dependent genetic switch regulates plant infection by the rice blast fungus. Proc Natl Acad Sci U S A, 107(50), 21902-21907. Abstract. Author URL.

TAYLOR SJC, MCCAGUE R, WISDOM R, LEE C, DICKSON K, RUECROFT G, O'BRIEN F, LITTLECHILD J, BEVAN J, ROBERTS SM, et al (2010). ChemInform Abstract: Development of the Biocatalytic Resolution of 2‐Azabicyclo(2.2.1)hept‐ 5‐en‐3‐one as an Entry to Single‐Enantiomer Carbocyclic Nucleosides. ChemInform, 24(41), no-no.

Opperman DJ, Sewell BT, Litthauer D, Isupov MN, Littlechild JA, van Heerden E (2010). Crystal structure of a thermostable old yellow enzyme from Thermus scotoductus SA-01. Biochem Biophys Res Commun, 393(3), 426-431. Abstract. Author URL.

Ngamsom B, Hickey AM, Greenway GM, Littlechild JA, Watts P, Wiles C (2010). Development of a high throughput screening tool for biotransformations utilising a thermophilic l-aminoacylase enzyme. Journal of Molecular Catalysis B: Enzymatic, 63(1-2), 81-86. Abstract.

Ngamsom B, Hickey AM, Greenway GM, Littlechild JA, McCreedy T, Watts P, Wiles C (2010). The development and evaluation of a conducting matrix for the electrochemical regeneration of the immobilised co-factor NAD(H) under continuous flow. Org Biomol Chem, 8(10), 2419-2424. Abstract. Author URL.

Willies S, Isupov M, Littlechild J (2010). Thermophilic enzymes and their applications in biocatalysis: a robust aldo-keto reductase. Environ Technol, 31(10), 1159-1167. Abstract. Author URL.

Rye CA, Isupov MN, Lebedev AA, Littlechild JA (2009). Biochemical and structural studies of a L-haloacid dehalogenase from the thermophilic archaeon Sulfolobus tokodaii. Extremophiles, 13(1), 179-190. Abstract. Author URL.

Littlechild J (2009). Thermophilic enzymes as stable biocatalysts. NEW BIOTECHNOLOGY, 25, S108-S108. Author URL.

Littlechild J (2008). Catalyst for improvement. EBR - European Biopharmaceutical Review(SUMM), 27-32. Abstract.

Ngamsom B, Marle L, Hickey AM, Greenway GM, Watts P, McCreedy T, Littlechild JA (2008). Immobilisation of thermophilic enzymes within miniaturised flow reactors for biotransformations. AIChE Annual Meeting, Conference Proceedings

Rye CA, Isupov MN, Lebedev AA, Littlechild JA (2007). An order-disorder twin crystal of L-2-haloacid dehalogenase from Sulfolobus tokodaii. Acta Crystallogr D Biol Crystallogr, 63(Pt 8), 926-930. Abstract. Author URL.

Battershill C, Bavington C, Chahal S, Jaspars M, Littlechild J, Spragg AM (2007). Contributions of marine bioscience to industrial biotechology. Industrial Biotechnology, 3(4), 304-313. Abstract.

Sayer C, Isupov MN, Littlechild JA (2007). Crystallization and preliminary X-ray diffraction analysis of omega-amino acid:pyruvate transaminase from Chromobacterium violaceum. Acta Crystallogr Sect F Struct Biol Cryst Commun, 63(Pt 2), 117-119. Abstract. Author URL.

Hickey AM, Marle L, McCreedy T, Watts P, Greenway GM, Littlechild JA (2007). Immobilization of thermophilic enzymes in miniaturized flow reactors. Biochem Soc Trans, 35(Pt 6), 1621-1623.

The exploitation of enzymes for biotransformation reactions for the production of new and safer drug intermediates has been the focus of much research. While a number of enzymes are commercially available, their use in an industrial setting is often limited to reactions that are cost-effective and they are rarely investigated further. However, the development of miniaturized flow reactor technology has meant that the cost of such research, once considered cost- and time-inefficient, would be much less prohibitive. The use of miniaturized flow reactors for enzyme screening offers a number of advantages over batch enzyme assay systems. Since the assay is performed on a miniaturized scale, enzyme, substrate and cofactor quantities are significantly reduced, thus reducing the cost of laboratory-scale investigations. Since flow reactors use microfluidic systems, where the substrate and products flow out of the system, the problems of substrate inhibition and product inhibition encountered by some enzymes are avoided. Quite often, enzymes fulfil a single-use function in biotransformation processes; however, enzyme immobilization allows enzyme reuse and often helps to increase enzyme stability. We have used an aminoacylase enzyme with potential use for industrial biotransformation reactions and have successfully immobilized it in miniaturized flow reactors. This L-aminoacylase is from the thermophilic archaeon Thermococcus litoralis. Two approaches to enzyme immobilization have been examined, both involving enzyme cross-linking. The first reactor type has used monoliths, to which the enzyme was attached, and the second contained previously cross-linked enzyme trapped using frits, in the microfluidic channels. Two different microreactor designs were used in the investigation: microreactor chips for the monoliths and capillary flow reactors for the cross-linked enzyme. These systems allowed passage of the substrate and product through the system while retaining the aminoacylase enzyme performing the catalytic conversion. The enzyme has been successfully immobilized and used to produce stable biocatalytic microreactors that can be used repeatedly over a period of several months.

Abstract. Author URL.

Littlechild JA, Guy J, Connelly S, Mallett L, Waddell S, Rye CA, Line K, Isupov M (2007). Natural methods of protein stabilization: thermostable biocatalysts. Biochem Soc Trans, 35(Pt 6), 1558-1563. Abstract. Author URL.

Littlechild J (2007). Nature's catalysts for biosynthesis of natural products. AMINO ACIDS, 33(3), XIV-XIV. Author URL.

Watts P, McCreedy T, Marle L, Littlechild J, Hickey AM, Greenway GM (2007). ORGN 104-The use of immobilized thermophilic enzymes for organic synthesis in flow reactors. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 234 Author URL.

Coupe EE, Smyth MG, Fosberry AP, Hall RM, Littlechild JA (2007). The dodecameric vanadium-dependent haloperoxidase from the marine algae Corallina officinalis: cloning, expression, and refolding of the recombinant enzyme. Protein Expr Purif, 52(2), 265-272. Abstract. Author URL.

Wilson RA, Jenkinson JM, Gibson RP, Littlechild JA, Wang Z-Y, Talbot NJ (2007). Tps1 regulates the pentose phosphate pathway, nitrogen metabolism and fungal virulence. The EMBO Journal, 26(15), 3673-3685.

Tapper S, Littlechild JA, Molard Y, Prokes I, Tucker JHR (2006). Anion binding tripodal receptors as structural models for the active site of vanadium haloperoxidases and acid phosphatases. Supramolecular Chemistry, 18(1), 55-58. Abstract.

Conklin PL, Gatzek S, Wheeler GL, Dowdle J, Raymond MJ, Rolinski S, Isupov M, Littlechild JA, Smirnoff N (2006). Arabidopsis thaliana VTC4 encodes L-galactose-1-P phosphatase, a plant ascorbic acid biosynthetic enzyme. J Biol Chem, 281(23), 15662-15670. Abstract. Author URL.

Littlechild J, Garcia-Rodriguez E, Isupov M (2006). INOR 398-Crystallization studies of vanadium haloperoxidases: Insights into halide specificity and enzyme mechanism. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 232 Author URL.

Garcia-Rodriguez E, Ohshiro T, Aibara T, Izumi Y, Littlechild J (2005). Enhancing effect of calcium and vanadium ions on thermal stability of bromoperoxidase from Corallina pilulifera. J Biol Inorg Chem, 10(3), 275-282. Abstract. Author URL.

Littlechild J (2005). Nature's catalysts and their applications in the pharmaceutical industry. EBR - European Biopharmaceutical Review(AUTUMN), 64-68. Abstract.

Connelly S, Line K, Isupov MN, Littlechild JA (2005). Synthesis and characterisation of a ligand that forms a stable tetrahedral intermediate in the active site of the Aureobacterium species (-) gamma-lactamase. Org Biomol Chem, 3(18), 3260-3262. Abstract. Author URL.

Clark DS, Ball P, Littlechild JA, Rice DW, Halle B (2004). Characteristics of nearly dry enzymes in organic solvents: Implications for biocatalysis in the absence of water. Philosophical Transactions of the Royal Society B: Biological Sciences, 359(1448), 1299-1307. Abstract.

Brice DC, Bryant JA, Dambrauskas G, Drury SC, Littlechild JA (2004). Cloning and expression of cytosolic phosphoglycerate kinase from pea (Pisum sativum L.). J Exp Bot, 55(398), 955-956. Abstract. Author URL.

Isupov MN, Brindley AA, Hollingsworth EJ, Murshudov GN, Vagin AA, Littlechild JA (2004). Crystallization and preliminary X-ray diffraction studies of a fungal hydrolase from Ophiostoma novo-ulmi. Acta Crystallogr D Biol Crystallogr, 60(Pt 10), 1879-1882. Abstract. Author URL.

Ohshiro T, Littlechild J, Garcia-Rodriguez E, Isupov MN, Iida Y, Kobayashi T, Izumi Y (2004). Modification of halogen specificity of a vanadium-dependent bromoperoxidase. Protein Sci, 13(6), 1566-1571. Abstract. Author URL.

Rand RP, Ho MW, Littlechild JA, Finney JL, Cupane A, Engberts JBFN (2004). Probing the role of water in protein conformation and function. Philosophical Transactions of the Royal Society B: Biological Sciences, 359(1448), 1277-1285. Abstract.

Littlechild JA, Isupov MN, Line K (2004). The crystal structure of a (-)?-lactamase from an Aureobacterium species reveals a tetrahedral intermediate in the active site. Journal of Molecular Biology, 338(3), 519-532.

Toogood HS, Brown RC, Line K, Keene PA, Taylor SJC, McCague R, Littlechild JA (2004). The use of a thermostable signature amidase in the resolution of the bicyclic synthon (rac)-γ-lactam. Tetrahedron, 60(3), 711-716. Abstract.

Halling PJ, Finney JL, Ho MW, Franks F, Littlechild JA (2004). What can we learn by studying enzymes in non-aqueous media?. Philosophical Transactions of the Royal Society B: Biological Sciences, 359(1448), 1287-1297. Abstract.

Guy JE, Isupov MN, Littlechild JA (2003). Crystallization and preliminary X-ray diffraction studies of a novel alcohol dehydrogenase from the hyperthermophilic archaeon Aeropyrum pernix. Acta Crystallogr D Biol Crystallogr, 59(Pt 1), 174-176. Abstract. Author URL.

Watts, A. Giles, G.I. Fry, F.H. (2003). Metal and Redox Regulation of Cysteine Protein Function. Chemistry and Biology, 10, 677-693.

Littlechild JA, Garcia-Rodriguez E (2003). Structural studies on the dodecameric vanadium bromoperoxidase from Corallina species. Coordination Chemistry Reviews, 237(1-2), 65-76.

Littlechild JA, Guy JE, Isupov MN (2003). The Structure of an Alcohol Dehydrogenase from the Hyperthermophilic Archaeon Aeropyrum pernix. Journal of Molecular Biology, 331(5), 1041-1051.

Watts AB, Beecher J, Whitcher CS, Littlechild JA (2002). A method for screening Baeyer-Villiger monooxygenase activity against monocyclic ketones. Biocatalysis and Biotransformation, 20(3), 209-215. Abstract.

Toogood HS, Hollingsworth EJ, Brown RC, Taylor IN, Taylor SJC, McCague R, Littlechild JA (2002). A thermostable L-aminoacylase from Thermococcus litoralis: cloning, overexpression, characterization, and applications in biotransformations. Extremophiles, 6(2), 111-122. Abstract. Author URL.

Hollingsworth EJ, Isupov MN, Littlechild JA (2002). Crystallization and preliminary X-ray diffraction analysis of L-aminoacylase from the hyperthermophilic archaeon Thermococcus litoralis. Acta Crystallogr D Biol Crystallogr, 58(Pt 3), 507-510. Abstract. Author URL.

Littlechild J (2002). Extremely versatile systems. Trends in Biotechnology, 20(8).

Gloyn AL, Noordam K, Willemsen MA, Watts AB, Littlechild JA, Ellard S, Hatterlsey AT (2002). Familial hyperinsulinism caused by a novel activating glucokinase mutation. DIABETES, 51, A260-A260. Author URL.

Toogood HS, Taylor IN, Brown RC, Taylor SJC, McCague R, Littlechild JA (2002). Immobilisation of the thermostable L-aminoacylase from Thermococcus litoralis to generate a reusable industrial biocatalyst. Biocatalysis and Biotransformation, 20(4), 241-249. Abstract.

Littlechild J, Garcia-Rodriguez E, Dalby A, Isupov M (2002). Structural and functional comparisons between vanadium haloperoxidase and acid phosphatase enzymes. J Mol Recognit, 15(5), 291-296. Abstract. Author URL.

Qi JF, Isupov MN, Littlechild JA, Anderson LE (2001). Chloroplast glyceraldehyde-3-P dehydrogenase contains a single disulfide bond located in the C-terminal extension to the B subunit. BIOCHEMISTRY, 40(29), 8615-8615. Author URL.

Littlechild JA, Anderson LE, Isupov MN, Qi JF (2001). Chloroplast glyceraldehydes-3-phosphate dehydrogenase contains a single disulfide bond located in the C-terminal extension to the B subunit. Journal of Biological Chemistry, 276(38), 35247-35252.

Harris JR, Schröder E, Isupov MN, Scheffler D, Kristensen P, Littlechild JA, Vagin AA, Meissner U (2001). Comparison of the decameric structure of peroxiredoxin-II by transmission electron microscopy and X-ray crystallography. Biochim Biophys Acta, 1547(2), 221-234. Abstract. Author URL.

Gonsalvez IS, Isupov MN, Littlechild JA (2001). Crystallization and preliminary X-ray analysis of a gamma-lactamase. Acta Crystallogr D Biol Crystallogr, 57(Pt 2), 284-286. Abstract. Author URL.

Turner NA, Gaskin DJ, Yagnik AT, Littlechild JA, Vulfson EN (2001). Enantioselectivity of recombinant Rhizomucor miehei lipase in the ring opening of oxazolin-5(4H)-ones. Protein Eng, 14(4), 269-278. Abstract. Author URL.

Littlechild JA, Isupov M (2001). Glyceraldehyde-3-phosphate dehydrogenase from Sulfolobus solfataricus. Methods Enzymol, 331, 105-117. Author URL.

Crowhurst G, McHarg J, Littlechild JA (2001). Phosphoglycerate kinases from bacteria and archaea. Methods Enzymol, 331, 90-104. Author URL.

Singleton MR, Littlechild JA (2001). Pyrrolidone carboxylpeptidase from Thermococcus litoralis. Methods Enzymol, 330, 394-403. Author URL.

Littlechild J, Isupov M, Garcia E (2001). Structural studies on the dodecameric vanadium containing bromoperoxidase from Corallina officinalis. JOURNAL OF INORGANIC BIOCHEMISTRY, 86(1), 67-67. Author URL.

Dalby AR, Tolan DR, Littlechild JA (2001). The structure of human liver fructose-1,6-bisphosphate aldolase. Acta Crystallogr D Biol Crystallogr, 57(Pt 11), 1526-1533. Abstract. Author URL.

Gonsalvez IS, Littlechild JA, Taylor S, Brown R (2000). Characterisation of a novel γ-lactamase enzyme used in the synthesis of an anti-HIV drug. Biochemical Society Transactions, 28(3), a75-a75.

Singleton MR, Taylor SJ, Parrat JS, Littlechild JA (2000). Cloning, expression, and characterization of pyrrolidone carboxyl peptidase from the archaeon Thermococcus litoralis. Extremophiles, 4(5), 297-303. Abstract. Author URL.

Schröder E, Littlechild JA, Lebedev AA, Errington N, Vagin AA, Isupov MN (2000). Crystal structure of decameric 2-Cys peroxiredoxin from human erythrocytes at 1.7 a resolution. Structure, 8(6), 605-615. Abstract. Author URL.

Schroder E, Littlechild JA, Lebedev AA, Errington N, Vagin AA, Isupov MN (2000). Crystal structure of decameric 2-Cys peroxiredoxin from human erythrocytes at 1.7 angstrom resolution (vol 8, pg 605, 2000). STRUCTURE, 8(12), U5-U5. Author URL.

Isupov MN, Dalby AR, Brindley AA, Izumi Y, Tanabe T, Murshudov GN, Littlechild JA (2000). Crystal structure of dodecameric vanadium-dependent bromoperoxidase from the red algae Corallina officinalis. J Mol Biol, 299(4), 1035-1049. Abstract. Author URL.

Bourne PC, Isupov MN, Littlechild JA (2000). The atomic-resolution structure of a novel bacterial esterase. Structure, 8(2), 143-151. Abstract. Author URL.

Charron C, Talfournier F, Isupov MN, Littlechild JA, Branlant G, Vitoux B, Aubry A (2000). The crystal structure of d-glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaeon Methanothermus fervidus in the presence of NADP(+) at 2.1 a resolution. J Mol Biol, 297(2), 481-500.

The crystal structure of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the archaeon Methanothermus fervidus has been solved in the holo form at 2.1 a resolution by molecular replacement. Unlike bacterial and eukaryotic homologous enzymes which are strictly NAD(+)-dependent, GAPDH from this organism exhibits a dual-cofactor specificity, with a marked preference for NADP(+) over NAD(+). The present structure is the first archaeal GAPDH crystallized with NADP(+). GAPDH from M. fervidus adopts a homotetrameric quaternary structure which is topologically similar to that observed for its bacterial and eukaryotic counterparts. Within the cofactor-binding site, the positively charged side-chain of Lys33 decisively contributes to NADP(+) recognition through a tight electrostatic interaction with the adenosine 2'-phosphate group. Like other GAPDHs, GAPDH from archaeal sources binds the nicotinamide moiety of NADP(+) in a syn conformation with respect to the adjacent ribose and so belongs to the B-stereospecific class of oxidoreductases. Stabilization of the syn conformation is principally achieved through hydrogen bonding of the carboxamide group with the side-chain of Asp171, a structural feature clearly different from what is observed in all presently known GAPDHs from bacteria and eukaryotes. Within the catalytic site, the reported crystal structure definitively confirms the essential role previously assigned to Cys140 by site-directed mutagenesis studies. In conjunction with new mutation results reported in this paper, inspection of the crystal structure gives reliable evidence for the direct implication of the side-chain of His219 in the catalytic mechanism. M. fervidus grows optimally at 84 degrees C with a maximal growth temperature of 97 degrees C. The paper includes a detailed comparison of the present structure with four other homologous enzymes extracted from mesophilic as well as thermophilic organisms. Among the various phenomena related to protein thermostabilization, reinforcement of electrostatic and hydrophobic interactions as well as a more efficient molecular packing appear to be essentially promoted by the occurrence of two additional alpha-helices in the archaeal GAPDHs. The first one, named alpha4, is located in the catalytic domain and participates in the enzyme architecture at the quaternary structural level. The second one, named alphaJ, occurs at the C terminus and contributes to the molecular packing within each monomer by filling a peripherical pocket in the tetrameric assembly.

Abstract. Author URL.

Dalby A, Dauter Z, Littlechild JA (1999). Crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate: mechanistic implications. Protein Sci, 8(2), 291-297. Abstract. Author URL.

Isupov MN, Fleming TM, Dalby AR, Crowhurst GS, Bourne PC, Littlechild JA (1999). Crystal structure of the glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaeon Sulfolobus solfataricus. J Mol Biol, 291(3), 651-660. Abstract. Author URL.

Schröder E, Isupov MN, Naran A, Littlechild JA (1999). Crystallization and preliminary X-ray analysis of human thioredoxin peroxidase-B from red blood cells. Acta Crystallogr D Biol Crystallogr, 55(Pt 2), 536-538. Abstract. Author URL.

Charron C, Talfournier F, Isupov MN, Branlant G, Littlechild JA, Vitoux B, Aubry A (1999). Crystallization and preliminary X-ray diffraction studies of D-glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaeon Methanothermus fervidus. Acta Crystallogr D Biol Crystallogr, 55(Pt 7), 1353-1355. Abstract. Author URL.

Singleton MR, Isupov MN, Littlechild JA (1999). Crystallization and preliminary X-ray diffraction studies of pyrrolidone carboxyl peptidase from the hyperthermophilic archaeon Thermococcus litoralis. Acta Crystallogr D Biol Crystallogr, 55(Pt 3), 702-703. Abstract. Author URL.

Bourne PC, Isupov MN, Littlechild JA (1999). Crystallization and preliminary x-ray diffraction studies of a novel bacterial esterase. Acta Crystallogr D Biol Crystallogr, 55(Pt 4), 915-917. Abstract. Author URL.

Littlechild J (1999). Haloperoxidases and their role in biotransformation reactions. Curr Opin Chem Biol, 3(1), 28-34. Abstract. Author URL.

McHarg J, Kelly SM, Price NC, Cooper A, Littlechild JA (1999). Site-directed mutagenesis of proline 204 in the 'hinge' region of yeast phosphoglycerate kinase. Eur J Biochem, 259(3), 939-945.

Site-specific mutants have been produced in order to investigate the role of proline 204 in the 'hinge' region of yeast phosphoglycerate kinase (PGK). This totally conserved proline has been shown to be the only cis-proline in the high resolution crystal structures of yeast, B. stearothermophilus, T. brucei and T. maritima PGK, and may therefore have a role in the independent folding of the two domains or in the 'hinge' bending of the molecule during catalysis. The residue was replaced by a histidine (Pro204His) and a phenylalanine (Pro204Phe), and the resulting proteins characterised by differential scanning calorimetry (DSC), circular dichroism (CD), tryptophan fluorescence emission and kinetic analysis. Although the secondary and tertiary structure of the Pro204His protein is generally similar to that of the wild-type enzyme as assessed by CD, the enzyme is less stable to heat and guanidinium chloride denaturation than the wild-type. In the denaturation experiments two transitions were observed for both the wild-type and the Pro204His mutant, as have been previously reported for yeast PGK [Missiakas, D. Betton, J.M. Minard, P. & Yon, J.M. (1990) Biochemistry 29, 8683-8689]. The first transition is accompanied by an increase in fluorescence intensity leading to a hyperfluorescent state, followed by the second, corresponding to a decrease in fluorescence intensity. However, for the Pro204His mutant, the first transition proceeded at lower concentrations of guanidinium chloride and the second transition proceeded to the same extent as for the wild-type protein, suggesting that sequence-distant interactions are more rapidly disrupted in this mutant enzyme than in the wild-type enzyme, while sequence-local interactions are disrupted in a similar way. The Michaelis constants (K(m)) for both 3-phospho-D-glycerate and ATP are increased only by three or fourfold, which confirms that, as expected, the substrate binding sites are largely unaffected by the mutation. However, the turnover and efficiency of the Pro204His mutant is severely impaired, indicating that the mechanism of 'hinge' bending is hindered. The Pro204Phe enzyme was shown to be significantly less well folded than the wild-type and Pro204His enzymes, with considerable loss of both secondary and tertiary structure. It is proposed that the proline residue at 204 in the 'hinge' region of PGK plays a role in the stability and catalytic mechanism of the enzyme.

Abstract. Author URL.

Crowhurst GS, Dalby AR, Isupov MN, Campbell JW, Littlechild JA (1999). Structure of a phosphoglycerate mutase:3-phosphoglyceric acid complex at 1.7 A. Acta Crystallogr D Biol Crystallogr, 55(Pt 11), 1822-1826. Abstract. Author URL.

Singleton M, Isupov M, Littlechild J (1999). X-ray structure of pyrrolidone carboxyl peptidase from the hyperthermophilic archaeon Thermococcus litoralis. Structure, 7(3), 237-244. Abstract. Author URL.

Fleming TM, Jones CE, Piper PW, Cowan DA, Isupov MN, Littlechild JA (1998). Characterization, crystallization and preliminary X-ray investigation of glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaeon Sulfolobus solfataricus. Acta Crystallogr D Biol Crystallogr, 54(Pt 4), 671-674. Abstract. Author URL.

McGhie EJ, Isupov MN, Schröder E, Littlechild JA (1998). Crystallization and preliminary X-ray diffraction studies of the oxygenating subunit of 3,6-diketocamphane monooxygenase from Pseudomonas putida. Acta Crystallogr D Biol Crystallogr, 54(Pt 5), 1035-1038. Abstract. Author URL.

Brindley AA, Dalby AR, Isupov MN, Littlechild JA (1998). Preliminary X-ray analysis of a new crystal form of the vanadium-dependent bromoperoxidase from Corallina officinalis. Acta Crystallogr D Biol Crystallogr, 54(Pt 3), 454-457. Abstract. Author URL.

Lewis G, Bevan J, Rawas A, McMichael P, Wisdom R, McCague R, Watson H, Littlechild J (1997). Crystallization and preliminary X-ray studies on Candida cylindracea lipase. Acta Crystallogr D Biol Crystallogr, 53(Pt 3), 348-351. Abstract. Author URL.

Yagnik AT, Littlechild JA, Turner NJ (1997). Molecular modelling studies of substrate binding to the lipase from Rhizomucor miehei. J Comput Aided Mol Des, 11(3), 256-264. Abstract. Author URL.

Bentley PA, Kroutil W, Littlechild JA, Roberts SM (1997). Preparation of polyamino acid catalysts for use in Julia asymmetric epoxidation. Chirality, 9(2), 198-202. Abstract.

Fleming T, Littlechild J (1997). Sequence and structural comparison of thermophilic phosphoglycerate kinases with a mesophilic equivalent. Comp Biochem Physiol a Physiol, 118(3), 439-451. Abstract. Author URL.

Isupov MN, Obmolova G, Butterworth S, BadetDenisot MA, Badet B, Polikarpov I, Littlechild JA, Teplyakov A (1997). Substrate binding is required for assembly of the active conformation of the catalytic site in Ntn amidotransferases: Evidence from the 1.8 angstrom crystal structure of the glutaminase domain of glucosamine 6-phosphate synthase (vol 4, pg 801, 1996). STRUCTURE, 5(5), 723-723. Author URL.

Piper PW, Emson C, Jones CE, Cowan DA, Fleming TM, Littlechild JA (1996). Complementation of a pgk deletion mutation in Saccharomyces cerevisiae with expression of the phosphoglycerate-kinase gene from the hyperthermophilic Archaeon Sulfolobus solfataricus. Curr Genet, 29(6), 594-596. Abstract. Author URL.

Dalby A, Rawas A, Watson HC, Littlechild JA (1996). Crystallisation and preliminary x-ray diffraction studies on human liver aldolase. Protein and Peptide Letters, 3(3), 207-212. Abstract.

Brabban AD, Littlechild J, Wisdom R (1996). Stereospecific γ-lactamase activity in a Pseudomonas fluorescens species. Journal of Industrial Microbiology, 16(1), 8-14. Abstract.

Mcharg J, Littlechild JA (1996). Studies with inhibitors of the glycolytic enzyme phosphoglycerate kinase for potential treatment of cardiovascular and respiratory disorders. J Pharm Pharmacol, 48(2), 201-205. Abstract. Author URL.

Dalby A, Littlechild JA (1996). Studies with type I aldolase to understand fructose intolerance and combat parasitic disease. J Pharm Pharmacol, 48(2), 214-217. Abstract. Author URL.

Isupov MN, Obmolova G, Butterworth S, Badet-Denisot MA, Badet B, Polikarpov I, Littlechild JA, Teplyakov A (1996). Substrate binding is required for assembly of the active conformation of the catalytic site in Ntn amidotransferases: evidence from the 1.8 a crystal structure of the glutaminase domain of glucosamine 6-phosphate synthase. Structure, 4(7), 801-810. Abstract. Author URL.

McGhie EJ, Littlechild JA (1996). The purification and crystallisation of 2,5-diketocamphane 1,2-monooxygenase and 3,6-diketocamphane 1,6-monooxygenase from Pseudomonas putida NCIMB 10007. Biochem Soc Trans, 24(1). Author URL.

Fleming TM, Jones CE, Piper PW, Cowan DA, Adams MWW, Littlechild JA (1996). The purification and crystallisation of phosphoglycerate kinase from the hyperthermophilic eubacterium thermotoga maritima. Protein and Peptide Letters, 3(3), 213-218. Abstract.

Jones CE, Fleming TM, Piper PW, Littlechild JA, Cowan DA (1995). Cloning and sequencing of a gene from the archaeon Pyrococcus furiosus with high homology to a gene encoding phosphoenolpyruvate synthetase from Escherichia coli. Gene, 160(1), 101-103. Abstract. Author URL.

Littlechild J, Turner N, Hobbs G, Lilly M, Rawas A, Watson H (1995). Crystallization and preliminary X-ray crystallographic data with Escherichia coli transketolase. Acta Crystallogr D Biol Crystallogr, 51(Pt 6), 1074-1076. Abstract. Author URL.

Rush C, Willetts A, Davies G, Dauter Z, Watson H, Littlechild J (1995). Purification, crystallisation and preliminary X-ray analysis of the vanadium-dependent haloperoxidase from Corallina officinalis. FEBS Lett, 359(2-3), 244-246. Abstract. Author URL.

Jones CE, Fleming TM, Cowan DA, Littlechild JA, Piper PW (1995). The phosphoglycerate kinase and glyceraldehyde-3-phosphate dehydrogenase genes from the thermophilic archaeon Sulfolobus solfataricus overlap by 8-bp. Isolation, sequencing of the genes and expression in Escherichia coli. Eur J Biochem, 233(3), 800-808. Abstract. Author URL.

Davies GJ, Gamblin SJ, Littlechild JA, Dauter Z, Wilson KS, Watson HC (1994). Structure of the ADP complex of the 3-phosphoglycerate kinase from Bacillus stearothermophilus at 1.65 A. Acta Crystallogr D Biol Crystallogr, 50(Pt 2), 202-209. Abstract. Author URL.

Littlechild JA, Watson HC (1993). A data-based reaction mechanism for type I fructose bisphosphate aldolase. Trends Biochem Sci, 18(2), 36-39. Abstract. Author URL.

Taylor SJ, McCague R, Wisdom R, Lee C, Dickson K, Ruecroft G, O'Brien F, Littlechild J, Bevan J, Roberts SM, et al (1993). Development of the biocatalytic resolution of 2-azabicyclo[2.2.1]hept-5-en-3-one as an entry to single-enantiomer carbocyclic nucleosides. Tetrahedron: Asymmetry, 4(6), 1117-1128. Abstract.

BARBER MD, GAMBLIN SJ, WATSON HC, LITTLECHILD JA (1993). SITE-DIRECTED MUTAGENESIS OF YEAST PHOSPHOGLYCERATE KINASE - ARGININE-65, ARGININE-121 AND ARGININE-168. FEBS LETTERS, 320(3), 193-197. Author URL.

Vellieux FM, Hajdu J, Verlinde CL, Groendijk H, Read RJ, Greenhough TJ, Campbell JW, Kalk KH, Littlechild JA, Watson HC, et al (1993). Structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma brucei determined from Laue data. Proc Natl Acad Sci U S A, 90(6), 2355-2359. Abstract. Author URL.

Davies GJ, Gamblin SJ, Littlechild JA, Watson HC (1993). The structure of a thermally stable 3-phosphoglycerate kinase and a comparison with its mesophilic equivalent. Proteins, 15(3), 283-289. Abstract. Author URL.

Joao HC, Williams RJ, Littlechild JA, Nagasuma R, Watson HC (1992). An investigation of large inhibitors binding to phosphoglycerate kinase and their effect on anion activation. Eur J Biochem, 205(3), 1077-1088. Abstract. Author URL.

Walker PA, Joâo HC, Littlechild JA, Williams RJ, Watson HC (1992). Characterisation of yeast phosphoglycerate kinase modified by mutagenesis at residue 21. Eur J Biochem, 207(1), 29-37. Abstract. Author URL.

Eisenberg D, Perutz MF, Buckingham AD, Graf L, Thornton J, Blow DM, Fersht AR, Karplus M, Johnson LN, Rippmann F, et al (1992). General discussion. Faraday Discussions, 93, 107-129.

Davies GJ, Gamblin SJ, Littlechild JA, Watson HC (1992). Purification, crystallization and preliminary X-ray analysis of the 3-phosphoglycerate kinase from Bacillus stearothermophilus. J Mol Biol, 227(4), 1263-1264. Abstract. Author URL.

Littlechild JA (1992). Structure and function. Nature, 359(6394), 448-449.

Graham HC, Williams RJ, Littlechild JA, Watson HC (1991). A proton-NMR study of a site-directed mutation (His388----Glu) in the interdomain region of yeast phosphoglycerate kinase. Implications for domain movement. Eur J Biochem, 196(2), 261-269. Abstract. Author URL.

Gamblin SJ, Davies GJ, Grimes JM, Jackson RM, Littlechild JA, Watson HC (1991). Activity and specificity of human aldolases. J Mol Biol, 219(4), 573-576. Abstract. Author URL.

Littlechild JA (1991). Protein crystallization: Magical or logical: can we establish some general rules?. Journal of Physics D: Applied Physics, 24(2), 111-118. Abstract.

Davies GJ, Littlechild JA, Watson HC, Hall L (1991). Sequence and expression of the gene encoding 3-phosphoglycerate kinase from Bacillus stearothermophilus. Gene, 109(1), 39-45. Abstract. Author URL.

Minard P, Bowen DJ, Hall L, Littlechild JA, Watson HC (1990). Site-directed mutagenesis of aspartic acid 372 at the ATP binding site of yeast phosphoglycerate kinase: over-expression and characterization of the mutant enzyme. Protein Eng, 3(6), 515-521. Abstract. Author URL.

Gamblin SJ, Cooper B, Millar JR, Davies GJ, Littlechild JA, Watson HC (1990). The crystal structure of human muscle aldolase at 3.0 a resolution. FEBS Lett, 262(2), 282-286. Abstract. Author URL.

Fairbrother WJ, Walker PA, Minard P, Littlechild JA, Watson HC, Williams RJ (1989). NMR analysis of site-specific mutants of yeast phosphoglycerate kinase. An investigation of the triose-binding site. Eur J Biochem, 183(1), 57-67.

Site-specific mutants of yeast phosphoglycerate kinase have been produced in order to investigate the roles of the 'basic-patch' residues, arginine 168 and histidine 170. The fully-conserved residue, arginine 168, has been replaced with a lysine (R168K) and a methionine (R168M) residue, while the non-conserved histidine 170 has been replaced with an aspartate (H170D). Comparison of the 500-MHz 1H-NMR spectra of the mutant proteins with that of wild-type phosphoglycerate kinase shows that the overall fold of the mutants remains essentially unaltered from that of the native enzyme. Results of NOE experiments indicate that there are only very minor changes in structure in the vicinity of the mutations. These mutations have also led to firm sequence-specific resonance assignments to histidines 62, 167 and 170. NMR studies of 3-phosphoglycerate binding show that decreasing the positive charge in the sequence 168-170 reduces the binding of this substrate (by about 15-fold and 4-fold for mutants R168M and H170D respectively). Mutant R168K binds 3-phosphoglycerate with an affinity about twofold less than that of the native enzyme. Significantly, the activity of mutant H170D, measured at saturating substrate concentrations, is unchanged from that of the wild-type enzyme. This indicates that this residue is not of major importance in the binding or reaction of 3-phosphoglycerate. The observation is in agreement with results obtained for the wild-type enzyme, which indicate that 3-phosphoglycerate interacts most strongly with histidine 62 and least strongly with histidine 170, as would be predicted from the X-ray crystal structure. Substitution of positively charged arginine 168 with neutral methionine (or positively charged lysine) does not cause a detectable change in the pKa values of the neighbouring histidine groups, in as much as they remain below 3. The results reported here indicate that the observed reduction in catalytic efficiency relates less to direct electrostatic effects than to the mutants' inability to undergo 3-phosphoglycerate-induced conformational changes.

Abstract. Author URL.

Fairbrother WJ, Hall L, Littlechild JA, Walker PA, Watson HC, Williams RJ (1989). Site-directed mutagenesis of histidine 62 in the 'basic patch' region of yeast phosphoglycerate kinase. FEBS Lett, 258(2), 247-250. Abstract. Author URL.

Walker PA, Littlechild JA, Hall L, Watson HC (1989). Site-directed mutagenesis of yeast phosphoglycerate kinase. The 'basic-patch' residue arginine 168. Eur J Biochem, 183(1), 49-55. Abstract. Author URL.

Wilson HR, Williams RJ, Littlechild JA, Watson HC (1988). NMR analysis of the interdomain region of yeast phosphoglycerate kinase. Eur J Biochem, 170(3), 529-538. Abstract. Author URL.

Bowen D, Littlechild JA, Fothergill JE, Watson HC, Hall L (1988). Nucleotide sequence of the phosphoglycerate kinase gene from the extreme thermophile Thermus thermophilus. Comparison of the deduced amino acid sequence with that of the mesophilic yeast phosphoglycerate kinase. Biochem J, 254(2), 509-517. Abstract. Author URL.

FAIRBROTHER WJ, HALL L, LITTLECHILD JA, WALKER PA, WATSON HC, WILLIAMS RJP (1988). PROBING THE 3-PHOSPHOGLYCERATE-BINDING SITE OF YEAST PHOSPHOGLYCERATE KINASE USING SITE-SPECIFIC MUTANTS AND H-1 NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY. BIOCHEMICAL SOCIETY TRANSACTIONS, 16(5), 724-725. Author URL.

FAIRBROTHER WJ, HALL L, LITTLECHILD J, MINARD P, WATSON HC, WILLIAMS RJP (1987). ANION BINDING STUDY OF YEAST PHOSPHOGLYCERATE KINASE BY NMR AND SITE-SPECIFIC MUTAGENESIS. PROTEIN ENGINEERING, 1(3), 261-261. Author URL.

FAIRBROTHER WJ, HALL L, LITTLECHILD JA, MINARD P, WATSON HC, WILLIAMS RJP (1987). ANION BINDING STUDY OF YEAST PHOSPHOGLYCERATE KINASE BY NUCLEAR-MAGNETIC-RESONANCE AND SITE-SPECIFIC MUTAGENESIS. BIOCHEMICAL SOCIETY TRANSACTIONS, 15(5), 868-869. Author URL.

BOWEN D, DAVIES G, GAMBLIN S, HALL L, LITTLECHILD J, WATSON HC (1987). PHOSPHOGLYCERATE KINASE - a TEST-BED SYSTEM FOR THE STUDY OF PROTEIN THERMOSTABILITY. PROTEIN ENGINEERING, 1(3), 242-242. Author URL.

Littlechild JA, Davies GJ, Gamblin SJ, Watson HC (1987). Phosphoglycerate kinase from the extreme thermophile Thermus thermophilus Crystallization and preliminary X-ray data. FEBS Letters, 225(1-2), 123-126. Abstract.

MINARD P, WALKER P, BOWEN D, DAVIES G, LITTLECHILD J, HALL L, WATSON HC (1987). THE USE OF SITE-DIRECTED MUTAGENESIS TO STUDY THE GLYCOLYTIC ENZYME PHOSPHOGLYCERATE KINASE. PROTEIN ENGINEERING, 1(3), 260-260. Author URL.

Littlechild J, Malcolm A, Paterakis K, Ackermann I, Dijk J (1987). The tertiary structure of salt-extracted ribosomal proteins from Escherichia coli as studied by proton magnetic resonance spectroscopy and limited proteolysis experiments. Biochim Biophys Acta, 913(2), 245-255. Abstract. Author URL.

Crout DHG, Littlechild J, Morrey SM (1986). Acetoin metabolism: Stereochemistry of the acetoin produced by the pyruvate decarboxylase of wheat germ and by the α-acetolactate decarboxylase of Klebsiella aerogenes. Journal of the Chemical Society, Perkin Transactions 1, 105-108. Abstract.

LITTLECHILD JA (1986). THE TYPE-II RESTRICTION ENZYMES HGIAI AND TAQI - PURIFICATION AND PROPERTIES. BIOCHEMICAL SOCIETY TRANSACTIONS, 14(2), 268-268. Author URL.

Dijk J, Littlechild JA, Freund AM, Pouyet J, Daune M, Provencher SW (1986). The secondary structure of salt-extracted ribosomal proteins from Escherichia coli as studied by circular dichroic spectroscopy. Biochim Biophys Acta, 874(2), 227-234. Abstract. Author URL.

Stöffler-Meilicke M, Epe B, Woolley P, Lotti M, Littlechild J, Stöffler G (1984). Location of protein S4 on the small ribosomal subunit of E. coli and B. stearothermophilus with protein- and hapten-specific antibodies. Mol Gen Genet, 197(1), 8-18. Abstract. Author URL.

Crout DHG, Littlechild J, Mitchell MB, Morrey SM (1984). Stereochemistry of the decarboxylation of α-acetolactate (2-hydroxy-2-methyl-3-oxobutanoate) by the acetolactate decarboxylase of Klebsiella aerogenes. Journal of the Chemical Society, Perkin Transactions 1, 2271-2276. Abstract.

Paterakis K, Littlechild J, Woolley P (1983). Structural and functional studies on protein S20 from the 30-S subunit of the Escherichia coli ribosome. Eur J Biochem, 129(3), 543-548. Abstract. Author URL.

Epe B, Woolley P, Steinhäuser KG, Littlechild J (1982). Distance measurement by energy transfer: the 3' end of 16-S RNA and proteins S4 and S17 of the ribosome of Escherichia coli. Eur J Biochem, 129(1), 211-219. Abstract. Author URL.

Wirth R, Littlechild J, Böck A (1982). Ribosomal protein S20 purified under mild conditions almost completely inhibits its own translation. Mol Gen Genet, 188(1), 164-166. Abstract. Author URL.

Paterakis K, Littlechild J (1982). Structural domains of ribosomal protein S8 and their relationship to ribosomal RNA binding. FEBS Lett, 149(2), 328-333. Abstract. Author URL.

Georgalis Y, Giri L, Littlechild JA (1981). Physical studies on the ribosomal protein S2 from the Escherichia coli 30S. Biochemistry, 20(5), 1061-1064. Abstract. Author URL.

Pawlik RT, Littlechild J, Pon C, Gualerzi C (1981). Purification and properties of Escherichia coli translational initiation factors. Biochemistry International, 2(4), 421-428.

LITTLECHILD JA, MALCOLM AL, SOWDEN BK (1980). COMPARATIVE STUDIES ON THE 30S RIBOSOMAL-PROTEINS FROM ESCHERICHIA-COLI AND BACILLUS-STEAROTHERMOPHILUS. EUROPEAN JOURNAL OF CELL BIOLOGY, 22(1), 133-133. Author URL.

Littlechild J (1980). Proton magnetic resonance studies of Escherichia coli ribosomal protein S16. FEBS Lett, 111(1), 51-55. Author URL.

LITTLECHILD JA, PATERAKIS K (1980). STRUCTURAL STABILITY OF SEVERAL PROTEINS ISOLATED FROM THE 30S-RIBOSOMAL SUBUNIT OF ESCHERICHIA-COLI. EUROPEAN JOURNAL OF CELL BIOLOGY, 22(1), 132-132. Author URL.

Littlechild J, Morrison CA, Bradbury EM (1979). Proton magnetic resonance studies of Escherichia coli ribosomal protein S4 and a C-terminal fragment of this protein. FEBS Lett, 104(1), 90-94. Author URL.

Dijk J, Littlechild J (1979). Purification of ribosomal proteins from Escherichia coli under nondenaturing conditions. Methods Enzymol, 59, 481-502. Author URL.

Khechinashvili NN, Koteliansky VE, Gogia ZV, Littlechild J, Dijk J (1978). A heat denaturation study of several ribosomal proteins from Escherichia coli by scanning microcalorimetry. FEBS Letters, 95(2), 270-272.

Littlechild JA, Malcolm AL (1978). A new method for the purification of 30S ribosomal proteins from Escherichia coli using nondenaturing conditions. Biochemistry, 17(16), 3363-3369. Abstract. Author URL.

OSTERBERG R, SJOBERG B, LILJAS A, GARRETT RA, LITTLECHILD J (1978). SMALL-ANGLE X-RAY-SCATTERING STUDY OF COMPLEXES OF INDIVIDUAL COMPONENTS FROM ESCHERICHIA-COLI RIBOSOMES. JOURNAL OF APPLIED CRYSTALLOGRAPHY, 11(OCT), 487-487. Author URL.

Österberg R, Sjöberg B, Littlechild J (1978). Small-angle X-ray scattering study of the proteins S1, S8, S15, S16, S20 from Escherichia coli ribosomes. FEBS Letters, 93(1), 115-119.

Osterberg R, Sjöberg B, Garrett RA, Littlechild J (1978). Small-angle X-ray titration of the complex formed between the ribosomal protein S4 and its 16S binding site, S4-RNA: a central core in the 30S subunit. Nucleic Acids Res, 5(10), 3579-3587. Abstract. Author URL.

Giri L, Littlechild J, Dijk J (1977). Hydrodynamic studies on the Escherichia coli robosomal proteins S8 and L6, prepared by two different methods. FEBS Lett, 79(2), 238-244. Author URL.

Morrison CA, Bradbury EM, Littlechild J, Dijk J (1977). Proton magnetic resonance studies to compare Escherichia coli ribosomal proteins prepared by two different methods. FEBS Lett, 83(2), 348-352. Author URL.

Österberg R, Sjöberg B, Garrett RA, Littlechild J (1977). Small-angle X-ray scattering study of the 16 S RNA binding protein S4 from Escherichia coli ribosomes. FEBS Letters, 73(1), 22-24.

Osterberg R, Sjöberg B, Garrett RA, Littlechild J (1977). Small-angle x-ray scattering study of the 16S RNA binding protein S4 from Escherichia coli ribosomes. FEBS Lett, 73(1), 25-28. Author URL.

Dijk J, Littlechild J, Garrett RA (1977). The RNA binding properties of "native" protein-protein complexes isolated from the Escherichia coli ribosome. FEBS Lett, 77(2), 295-300. Author URL.

Littlechild J, Dijk J, Garrett RA (1977). The identification of new RNA-binding proteins in the Escherichia coli ribosome. FEBS Lett, 74(2), 292-294. Author URL.

Littlechild J (1973). Nuclease contaminant of a batch of lysozyme used for ribosome extraction: cleavage of Escherichia coli 23S rRNA into two specific fragments. Anal Biochem, 55(2), 634-636. Author URL.

Littlechild J, Spencer M (1973). Stability and homogeneity of preparations of ribosomal particles from Escherichia coli. Biochemistry, 12(16), 3102-3108. Author URL.

Chapters

Littlechild J, Isupov M (2014). Haloperoxidase enzymes as 'redox catalysts' important for industrial biocatalysis. In (Ed) Recent Advances in Redox Active Plant and Microbial Products: from Basic Chemistry to Widespread Applications in Medicine and Agriculture, 425-446. Abstract.

Novak H, Littlechild J (2013). 4 Marine enzymes with applications for biosynthesis of fine chemicals. In (Ed) Marine Enzymes for Biocatalysis, 89-106.

Littlechild JA (2013). Chapter 2 Protein structure and function. In (Ed) Introduction to Biological and Small Molecule Drug Research and Development, 57-79.

James PBC, sayer C, Novak H, Littlechild JA (2013). Mechanisms of Thermal Stability Adopted by Thermophilic Proteins and Their Use in White Biotechnology. In Littlechild JA, Satyanarayana T, Kawarabayasi Y (Eds.) Thermophilic Microbes in Environmental and Industrial Biotechnology, Springer Netherlands, 481-507.

Littlechild JA, Hill A (2012). Oxidation:Haloperoxidases. In Carreira EM, Yamamoto H (Eds.) Comprehensive Chirality, Amsterdam: Elsevier, 329-349. Abstract.

Szabo K, Gutowski NJ, Holley JE, Littlechild JA, Winyard P (2009). Redox Control in Human Disease with a Special Emphasis on the Peroxiredoxin-Based Antioxidant System. In Jacob C, Winyard PG (Eds.) Redox signaling and regulation in biology and medicine, Vch Verlagsgesellschaft Mbh, 409-431. Abstract.

Szabo KE, Line K, Eggleton P, Littlechild JA, Winyard P (2009). Structure and Function of the Human Peroxiredoxin-Based Antioxidant System:the Interplay between Peroxiredoxins,Thioredoxins,Thioredoxin Reductases,Sulfiredoxins and Sestrins. In Jacob C, Winyard PG (Eds.) Redox signaling and regulation in biology and medicine, Vch Verlagsgesellschaft Mbh, 143-174. Abstract.

Szabo KE, Line K, Eggleton P, Littlechild JA, Winyard PG (2009). Structure and function of the human peroxiredoxin-based antioxidant system: the interplay between peroxierdoxins, thioredoxins, thioredoxin reductases, sulfiredoxins and sestrins. In Jacob C, Winyard PG (Eds.) Redox Signaling and Regulation in Biology and Medicine, Weinheim, Germany: Wiley-VCH.

Littlechild JA, Garcia-Rodriguez E, Coupe E, Watts A, Isupov M (2007). Structural Studies of Vanadium Haloperoxidases:Insight into Halide Specificity,Stability and Enzyme Mechanism. In Kustin K, Pessoa JC, Crans D (Eds.) Vanadium:The versatile Metal, Washington, USA: ACS, 136-147.

Littlechild J, Garcia-Rodriguez E, Watts A, Coupe E, Isupov M (2007). The vanadium dependent bromoperoxidase enzymes:Insights into Mechanism and Applications gained from Structural Studies. In Aureliano M (Ed) Vanadium biochemistry, India: Signpost, 97-116.

Littlechild JA, Garcia-Rodriguez E, Watts A, Coupe E, Isupov M (2007). The vanadium dependent bromoperoxidase enzymes:Insights into Mechanism and Applications gained from Structural Studies. In Alves MA (Ed) Vanadium Biochemistry, India: Research Signpost, 97-116.

Conferences

Littlechild J (2018). Thermophilic enzymes for synthetic biology in vivo and in vitro cascades. Author URL.

Littlechild J (2016). Novel enzymes from metagenomics. Author URL.

Szabo-Taylor KE, Lo Faro ML, Eggleton P, Turner CAL, Tarr JM, Haigh RC, Littlechild JA, Whiteman M, Winyard PG (2010). Peroxiredoxin 2 in Human Inflammatory Joint Disease. Author URL.

Turner CA, Szabo KE, Haigh R, Tarr J, Littlechild JA, Eggleton P, Winyard PG (2009). EXPRESSION OF THE PEROXIREDOXIN-BASED ANTIOXIDANT SYSTEM IN PERIPHERAL BLOOD LYMPHOCYTES IN RHEUMATOID ARTHRITIS. Author URL.

Gutowski NJ, Watson EL, Holley JE, Winyard PG, Littlechild JA (2009). Peroxiredoxin II: an antioxidant with therapeutic potential in multiple sclerosis?. Author URL.

Szabo K, Tarr J, Eggleton P, Line K, Ryan B, Aksu K, Akcay Y, Haigh R, Littlechild J, Winyard P, et al (2008). Extracellular peroxiredoxin II in rheumatoid arthritis and other autoimmune conditions. Author URL.

Taylor IN, Brown RC, Bycroft M, King G, Littlechild JA, Lloyd MC, Praquin C, Toogood HS, Taylor SJC (2004). Application of thermophilic enzymes in commercial biotransformation processes. Abstract. Author URL.

Littlechild JA, Guy JE, Isupov MN (2004). Hyperthermophilic dehydrogenase enzymes. Abstract. Author URL.

Whitcher CS, Littlechild JA, Woodley JM (2003). Application of a Baeyer-Villiger monooxygenase from cunninghamella echinulata NRRL 3655. Author URL.

Gonsalvez IS, Littlechild JA, Isupov M, Taylor SJ, Brown R (2000). Characterisation and preliminary crystallographic studies of a novel γ-lactamase enzyme used in the synthesis of an anti-HIV drug.

Hollingsworth EJ, Brown R, Isupov MN, Taylor S, Littlechild JA (2000). Cloning, Expression & Purification of a Thermostable Aminoacylase from <i>Thermococcus litoralis</i>.

Schröder E, Littlechild JA, Lebedev AA, Isupov MN (2000). Structure and mechanism of decameric 2-cys peroxiredoxin from human erythrocytes.

Schröder E, Lebedev AA, Isupov MN, Littlechild JA (2000). Structure and mechanism of human decameric 2-cys peroxiredoxin.

Isupov MN, Dalby AR, Brindley AA, Littlechild JA (1999). CRYSTAL STRUCTURE OF THE VANADIUM DEPENDENT HALOPEROXIDASE FROM C. OFFICINALIS. Author URL.

Bourne PC, Isupov MN, Littlechild JA (1999). THE ATOMIC RESOLUTION (1.15 angstrom) STRUCTURE OF a NOVEL BACTERIAL ESTERASE. Author URL.

Schroder E, Isupov MI, Littlechild JA (1999). X-RAY STRUCTURAL STUDIES WITH HUMAN THIOREDOXIN PEROXIDASE. Author URL.

Isupov MN, Lebedev AA, Harutyunyan EH, Antson FA, Wilson KS, Dodson GG, Zakomirdina LN, Littlechild JA, Dementieva IS (1999). X-RAY STUDIES OF TRYPTOPHANASE. Author URL.

Crowhurst G, Isupov MN, Littlechild JA (1999). X-RAY STUDIES OF TWO GLYCOLYTIC ENZYMES FROM THE ARCHAEON SULFOLOBUS SOLFATARICUS. Author URL.

Crowhurst GS, Isupov MN, Fleming T, Littlechild JA (1998). Two glycolytic enzymes from Sulfolobus solfataricus. Author URL.

Dalby A, Rush C, Willetts A, Davies G, Dauter Z, Littlechild J (1996). ANALYSIS OF THE VANADIUM DEPENDENT HALOPEROXIDASE FROM CORALLINA OFFICINALIS. Author URL.

Lilly MD, Chauhan R, French C, Gyamerah M, Hobbs GR, Humphrey A, Isupov M, Littlechild JA, Mitra RK, Morris KG, et al (1996). Carbon-carbon bond synthesis: the impact of rDNA technology on the production and use of E. coli transketolase. Abstract.

McGhie EJ, Littlechild JA (1996). The purification and crystallisation of 2,5-diketocamphane 1,2 monooxygenase and 3,6-diketocamphane 1,6 monooxygenase from Pseudomonas putida NCIMB 10007.

Watson HC, Littlechild JA (1990). Isoenzymes of phosphoglycerate kinase: evolutionary conservation of the structure of this glycolytic enzyme. Author URL.

Publications by year

In Press

Littlechild JA (In Press). Improving the ‘Tool Box’ for Robust Industrial Enzymes. Journal of Industrial Microbiology & Biotechnology

2022

Frustaci S (2022). A Whispering Gallery Mode based sensor platform for single enzyme real time conformational changes.

Understanding the conformational changes that occur in an enzyme during turnover is crucial for understanding biomolecular processes and for new rational drug discovery. Many single-molecule techniques have been developed in the past three decades, such as Förster resonance energy transfer, although powerful, these techniques have their limitations, for example, limited temporal resolution, or necessity for fluorescent labelling. In this study a new class of highly sensitive optical devices based on the whispering gallery mode sensor have been investigated and employed to track the conformational changes of a kinase enzyme in real time.
A thermostable Geobacillus stearothermophilus phosphoglycerate kinase enzyme has been used as model enzyme to prove that the optoplasmonic whispering gallery mode sensor can detect the conformational changes involved in enzyme turnover.
The enzyme was expressed and purified to a high degree of purity that was suitable for crystallographic studies as well as biochemical investigation. The purified enzyme has been used for kinetics and biophysical enzymatic characterisation. A reproducible protocol has been established to immobilise the enzyme onto gold nanoparticles in a defined orientation to track the conformational changes occurring on the sensor. The enzyme has been immobilised onto the gold nanoparticles using two different methods: through the his-tags introduced onto the recombinant enzyme and directly onto the gold through a surface cysteine residue introduced by site-directed mutagenesis. The kinase enzyme was found to retain activity using both methods.
To rationalise the observed conformational changes occurring during enzymatic turnover, the crystal structures of the native enzyme and its complexes with the substrate, and with substrate together with non-hydrolysable ATP, have been determined to high resolution, between 1.2 Å and 2 Å. Finally, for the first-time a real-time visualisation of the movement of the phosphoglycerate kinase during enzymatic turnover has been recorded. Repeating signals from the sensor were registered and only observed when both the substrate 3-phosphoglycerate and ATP are introduced with the enzyme into the sensor chamber. No signal is observed with the 3-phosphoglycerate alone or ATP alone or when 3-phosphoglycerate and a non-hydrolysable ATP analogue were used with the enzyme. The sensor system presented in this thesis shows potential for future fast, real-time, rapid throughput, lab-on-chip measurements for studying single enzymes.

Abstract.

Wohlgemuth R, Littlechild J, Kim B-G (2022). Editorial: Systems biocatalysis for bioprocess design. Frontiers in Bioengineering and Biotechnology, 10

Cutlan R (2022). Synthetic Biology for Green Chemistry: Building in Vivo Enzymatic Cascades Using Carboxylic Acid Reductases (CARs).

Biocatalysis has a proven track record of offering replacements for individual chemical reactions with a lower environmental impact. Cascade reactions are an extension of biocatalysis; coupling a series of reactions to provide replacement for more than one chemical step. Herein, this thesis describes the engineering of a multi-enzyme cascade reaction for the production of phenylacetylcarbinol (PAC). Using a carboxylic acid reductase (CAR) from Mycobacterium phlei and a pyruvate decarboxylase from Acetobacter pasteurianus this thesis demonstrated a biocatalytic cascade reaction in which benzoic acid and pyruvate are converted into PAC. This cascade was combined with several other enzymes to recycle spent cofactors and deplete inhibitor by-products.
Furthermore, this thesis has highlighted the discovery of five putative enzymes; three ancestral CARs (AncCARs) and two thiamine diphosphate (ThDP) dependent enzymes. CARs typically have poor stability and thus limited tractability in industrial reactions. Within this study ancestral sequence reconstruction was performed on type I CARs. This is a developing engineering tool that can identify stabilizing and enzymatically neutral mutations throughout a protein. A combined algorithm approach was used to reconstruct functional ancestors of the Mycobacterial and Nocardial Type I CAR orthologues. Carboxylic acid reduction by Ancestral CARs was confirmed. Each showed a preference for aromatic carboxylic acids. AncCARs also showed improved tolerance to solvents, pH and in vivo-like salt-like conditions. Compared to well-studied extant CARs, AncCARs had a Tm up to 35 °C higher. Two ThDP enzymes were discovered using metagenomics. These were assessed in silico through homology modelling and docking simulations. Furthermore, this study has demonstrated the importance of each tool in the discovery of new enzymes from within the ThDP family. Our homology models were used in docking simulations with unique carboligation-like intermediates allowing a rationalization of the reactions and stereoisomerism of the products. Two functional enzymes ThDP enzymes were identified that are capable of producing PAC; one from Thermus thermophilus and another from bacterium HR16.

Abstract.

2021

De Rose SA, Harmer N, Littlechild J (2021). Production of the extremolyte cyclic 2,3-diphosphoglycerate using Thermus thermophilus as a whole-cell factory. Abstract.

De Rose S, Harmer N, Littlechild J, Finnigan W (2021). Production of the extremolyte cyclic 2,3-diphosphoglycerate using Thermus thermophilus as a whole-cell factory- DATASET.

2020

K. Hussain K, Malavia D, M. Johnson E, Littlechild J, Winlove CP, Vollmer F, Gow NAR (2020). Biosensors and Diagnostics for Fungal Detection. Journal of Fungi, 6(4), 349-349. Abstract.

2019

finnigan W, Cutlan R, Snajdrova R, Adams J, Littlechild J, Harmer NJ (2019). Engineering a Seven Enzyme Biotransformation using Mathematical Modelling and Characterized Enzyme Parts (dataset).

Finnigan W, Cutlan R, Snajdrova R, Adams JP, Littlechild JA, Harmer NJ (2019). Engineering a seven enzyme biotransformation using mathematical modelling and characterized enzyme parts.

Kalibala R (2019). Investigation into Human Erythrocyte Peroxiredoxin 2 : S-Nitrosation and Interaction with Haemoglobin.

The most abundant intracellular protein in erythrocytes is haemoglobin (Hb) and the third most abundant protein is peroxiredoxin 2 (Prx2). Prx2 exists in both dimeric and decameric form; its dimeric form has two cysteines (Cys) redox active sites. The presence of the two redox-active Cys sites means that Prx2 possesses free thiols, which can react with reactive nitrogen species to form S-nitrosothiols. The function of Prx2 is not completely understood, although it is thought to be an antioxidant by virtue of its peroxidase activity. Prx2 may play a central role in protecting Hb against oxidative damage and mediating some of the key functions of Hb. Nitric oxide (NO) exerts numerous important physiological functions in biological systems including vasodilation in humans. Because of the short-lived nature of NO, S-nitrosothiols (RSNOs) are believed to act as stable NO carriers.
This study hypothesises a model highlighting possible interactions between NO and Hb, and the HbNO complex and Prx2. In this model, NO is produced upon nitrite reduction by deoxyHb, NO equivalents are transferred to the Cys residues of Prx2 forming S-nitrosoperoxiredoxin (Prx2-SNO). The proximity of Prx2 to Hb promotes S-nitrosothiol formation in Prx2 and avoids the scavenging of NO by Hb itself.
This study also describes the purification of the native hPrx2, and the over-expression and purification of hPrx2 in various forms, as well as the subsequent crystallisation and X-ray diffraction studies. The calibrated gel filtration column confirmed that hPrx2 is mainly produced in the decameric form. Purification of native hPrx2 isolated from human red blood cells (RBCs) was successfully achieved using FFQ Sepharose and gel filtration chromatography (Superdex 200). The recombinant hPrx2 DNA cloned in pET28q was transformed into a competent E.coli Rosetta Gami 2 cell line. The purified recombinant hPrx2 protein was achieved using nickel affinity and gel filtration column chromatography. S-nitrosated Prx2 (Prx2-SNO) was achieved by incubation of Prx2 with S-nitrosoglutathione (GSNO) under differing experimental conditions. The mixing of hPrx2 and Hb in various molar ratios, demonstrated a significant specific protein-protein interaction between a Prx2 decamer with an Hb tetramer. The complex binding results from size exclusion chromatography showed that decameric Prx2 bound to Hb in a 1:1 ratio.
This study also describes the post-modification of hPrx2 cysteine residues, and the nitration of tyrosine residues attained by the incubation of protein with GSNO. The incubation of the recombinant hPrx2 protein with GSNO altered the oligomeric state of hPrx2 into a dimer formation. The gas-phase chemiluminescence, gel filtration chromatography, Saville assay, Western-blot, UV-vis spectrophotometry and LC-MS/MS, confirmed the post-modifications of the protein residues.
This research reports the purification and characterization of the stable; native hPrx2, recombinant hPrx2, hPrx2-SNO, and SNO-Hb proteins necessary to perform the hypothesised interactions, to allow us to understand the transnitrosation process that could occur between hPrx2 and Hb. The study also describes the crystallisation conditions for hPrx2-Hb complex and the co-crystallisation conditions for hPrx2-SNO and [hPrx2-SNO]Hb complex

Abstract.

Westlake A (2019). Thermostable Enzymes Important for Industrial Biotechnology.

The use of enzymes in technology is of increasing commercial interest due to their high catalytic efficiency and specificity and the lowering of manufacturing costs. Enzymes are also becoming more widely utilised because they are more environmentally friendly compared to chemical methods. Firstly, they carry out their reactions at ambient temperatures requiring less energy to achieve the high temperatures and pressures that many chemical methods require. Secondly, they can substitute for toxic chemical catalysts which need careful disposal. In this project two classes of enzymes of industrial interest from thermophiles were investigated, lactonase enzymes and 1-deoxy-D-xylulose 5-phosphate (DXP) synthases.

A quorum sensing lactonase from Vulcanisaeta moutnovskia, a thermoacidophilic anaerobic crenarchaeon, was expressed in high levels in an Escherichia coli host, then purified and characterised with a range of industrially relevant substrates. These enzymes are of industrial interest for water treatment and bioreactors for their ability to prevent biofilm formation in bacteria. This enzyme showed different specificity to another well characterised quorum sensing lactonase from a thermophilic crenarchaeon, Sulfolobus solfataricus. Crystals of the native enzyme were obtained. Structural examination revealed that the V. moutnovskia lactonase possesses an α-helix obstructing a hydrophobic channel near the active site, whereas the S. solfataricus lactonase has a flexible loop leaving the hydrophobic channel unrestricted. As a result the acyl chains of substrates interact with surface residues of the α-helix in V. moutnovskia lactonase rather than sitting in the channel, so its activity is no longer restricted to substrates with long acyl chains.

A gluconolactonase encoded by a thermophilic Planctomyces genome was cloned and expressed at high levels in an E. coli host, purified and successfully crystallised. The crystals had a space group of P 3 2 1 and diffracted to a resolution of 2.41 Å. This enzyme was intended to be used by an industrial partner for synthesis of metabolite standards for mass spectrometry and diagnostics. Attempts were made to clone, purify and express two other lactonases from thermophilic metagenomes obtained from terrestrial hot springs: an enol lactonase and a second quorum sensing lactonase. Homology modelling was used to create predicted structures for both of these enzymes. The quorum sensing lactonase showed a 2.5 Å difference in the position of a catalytic serine and a 3.1 Å difference in a catalytic histidine in comparison to a mesophilic homologue. The enol lactonase contained an aspartic acid in place of a catalytic serine found in a mesophilic homologue.

A DXP synthase from an anaerobic Gram-negative bacterium Thermovibrio ammonificans was successfully cloned, over-expressed and purified. Crystals were successfully produced although these diffracted only to low resolution. A DXP synthase from an anaerobic Gram-positive bacterium Carboxydothermus hydroformans was successfully cloned, however the protein was expressed primarily in the insoluble fraction. Homology models were made for these two enzymes. Both enzymes showed strong similarity with mesophilic DXP synthases in terms of tertiary structure and positions of active site residues. Visual analysis revealed an increase of 15-20 % in the number of hydrophobic interactions within the enzymes and a high proportion of charged residues at the dimer interface, which would confer increased thermostability. The hope was to obtain high resolution diffraction data to assist in understanding what allows these enzymes to utilise pyruvate as a substrate compared to transketolase, a related enzyme, which uses hydroxypyruvate.

Abstract.

2018

Littlechild J (2018). Thermophilic enzymes for synthetic biology in vivo and in vitro cascades. Author URL.

2017

Littlechild JA, Isupov MN (2017). Comments to Article by Willetts A. et al. Microorganisms 2016, 4, 38. Microorganisms, 5(3). Abstract. Author URL.

de Rose SA, Novak H, Dowd A, Singh S, Lang DA, Littlechild J (2017). Stabilization of a lipolytic enzyme for commercial application. Catalysts, 7(3). Abstract.

2016

Littlechild J (2016). Novel enzymes from metagenomics. Author URL.

2015

Littlechild JA (2015). Archaeal Enzymes and Applications in Industrial Biocatalysts. Archaea, 2015, 1-10. Abstract.

Littlechild JA (2015). Enzymes from Extreme Environments and Their Industrial Applications. Front Bioeng Biotechnol, 3 Abstract. Author URL.

2014

Vivoli M, Novak HR, Littlechild JA, Harmer NJ (2014). Determination of Protein-ligand Interactions Using Differential Scanning Fluorimetry. Journal of Visualized Experiments(91).

Vivoli M, Novak HR, Littlechild JA, Harmer NJ (2014). Determination of protein-ligand interactions using differential scanning fluorimetry. J Vis Exp(91). Abstract. Author URL.

Littlechild J, Sayer C, Isupov M, Ward J, Littlechild J (2014). Structural studies on transaminase enzymes and applications in biocatalysis. NEW BIOTECHNOLOGY, 31, S19-S19. Author URL.

2013

Novak H, Littlechild J (2013). 4 Marine enzymes with applications for biosynthesis of fine chemicals. In (Ed) Marine Enzymes for Biocatalysis, 89-106.

Littlechild JA (2013). Chapter 2 Protein structure and function. In (Ed) Introduction to Biological and Small Molecule Drug Research and Development, 57-79.

Hill A, Littlechild J (2013). ChemInform Abstract: Oxidation. Haloperoxidases. ChemInform, 44(25), no-no.

Novak H, Littlechild J (2013). Marine enzymes with applications for biosynthesis of fine chemicals. , 89-106. Abstract.

Satyanarayana T, Littlechild J, Kawarabayasi Y (2013). Preface.

Littlechild JA (2013). Protein structure and function. , 57-79. Abstract.

2012

Hill A, Littlechild J (2012). 7.15 Oxidation: Haloperoxidases. , 7, 329-349. Abstract.

Littlechild JA, Greenway G, Watts P, Hickey AM, Ngamsom B (2012). Immobilised Enzymes and Co-Factors.

Littlechild JA, Hill A (2012). Oxidation:Haloperoxidases. In Carreira EM, Yamamoto H (Eds.) Comprehensive Chirality, Amsterdam: Elsevier, 329-349. Abstract.

2011

Littlechild JA (2011). Thermophilic archaeal enzymes and applications in biocatalysis. Biochem Soc Trans, 39(1), 155-158. Abstract. Author URL.

2010

Szabo-Taylor KE, Lo Faro ML, Eggleton P, Turner CAL, Tarr JM, Haigh RC, Littlechild JA, Whiteman M, Winyard PG (2010). Peroxiredoxin 2 in Human Inflammatory Joint Disease. Author URL.

Willies S, Isupov M, Littlechild J (2010). Thermophilic enzymes and their applications in biocatalysis: a robust aldo-keto reductase. Environ Technol, 31(10), 1159-1167. Abstract. Author URL.

2009

Gutowski NJ, Watson EL, Holley JE, Winyard PG, Littlechild JA (2009). Peroxiredoxin II: an antioxidant with therapeutic potential in multiple sclerosis?. Author URL.

Littlechild J (2009). Thermophilic enzymes as stable biocatalysts. NEW BIOTECHNOLOGY, 25, S108-S108. Author URL.

2008

Littlechild J (2008). Catalyst for improvement. EBR - European Biopharmaceutical Review(SUMM), 27-32. Abstract.

Ward S, Macgowan A, Roberts S, Littlechild JA, Line K, Irving E, Donnelly S (2008). Derivatives of 18Beta-Glycyrrhetinic Acid.

2007

Hickey AM, Marle L, McCreedy T, Watts P, Greenway GM, Littlechild JA (2007). Immobilization of thermophilic enzymes in miniaturized flow reactors. Biochem Soc Trans, 35(Pt 6), 1621-1623.

Abstract. Author URL.

Littlechild J (2007). Nature's catalysts for biosynthesis of natural products. AMINO ACIDS, 33(3), XIV-XIV. Author URL.

2006

2005

Littlechild J (2005). Nature's catalysts and their applications in the pharmaceutical industry. EBR - European Biopharmaceutical Review(AUTUMN), 64-68. Abstract.

2004

Littlechild JA, Guy JE, Isupov MN (2004). Hyperthermophilic dehydrogenase enzymes. Abstract. Author URL.

2003

Whitcher CS, Littlechild JA, Woodley JM (2003). Application of a Baeyer-Villiger monooxygenase from cunninghamella echinulata NRRL 3655. Author URL.

Watts, A. Giles, G.I. Fry, F.H. (2003). Metal and Redox Regulation of Cysteine Protein Function. Chemistry and Biology, 10, 677-693.

Littlechild JA, Garcia-Rodriguez E (2003). Structural studies on the dodecameric vanadium bromoperoxidase from Corallina species. Coordination Chemistry Reviews, 237(1-2), 65-76.

Littlechild JA, Guy JE, Isupov MN (2003). The Structure of an Alcohol Dehydrogenase from the Hyperthermophilic Archaeon Aeropyrum pernix. Journal of Molecular Biology, 331(5), 1041-1051.

2002

Littlechild J (2002). Extremely versatile systems. Trends in Biotechnology, 20(8).

2001

Littlechild JA, Isupov M (2001). Glyceraldehyde-3-phosphate dehydrogenase from Sulfolobus solfataricus. Methods Enzymol, 331, 105-117. Author URL.

Crowhurst G, McHarg J, Littlechild JA (2001). Phosphoglycerate kinases from bacteria and archaea. Methods Enzymol, 331, 90-104. Author URL.

Singleton MR, Littlechild JA (2001). Pyrrolidone carboxylpeptidase from Thermococcus litoralis. Methods Enzymol, 330, 394-403. Author URL.

Dalby AR, Tolan DR, Littlechild JA (2001). The structure of human liver fructose-1,6-bisphosphate aldolase. Acta Crystallogr D Biol Crystallogr, 57(Pt 11), 1526-1533. Abstract. Author URL.

2000

Hollingsworth EJ, Brown R, Isupov MN, Taylor S, Littlechild JA (2000). Cloning, Expression & Purification of a Thermostable Aminoacylase from <i>Thermococcus litoralis</i>.

Schröder E, Littlechild JA, Lebedev AA, Isupov MN (2000). Structure and mechanism of decameric 2-cys peroxiredoxin from human erythrocytes.

Schröder E, Lebedev AA, Isupov MN, Littlechild JA (2000). Structure and mechanism of human decameric 2-cys peroxiredoxin.

Bourne PC, Isupov MN, Littlechild JA (2000). The atomic-resolution structure of a novel bacterial esterase. Structure, 8(2), 143-151. Abstract. Author URL.

Abstract. Author URL.

1999

Isupov MN, Dalby AR, Brindley AA, Littlechild JA (1999). CRYSTAL STRUCTURE OF THE VANADIUM DEPENDENT HALOPEROXIDASE FROM C. OFFICINALIS. Author URL.

Littlechild J (1999). Haloperoxidases and their role in biotransformation reactions. Curr Opin Chem Biol, 3(1), 28-34. Abstract. Author URL.

McHarg J, Kelly SM, Price NC, Cooper A, Littlechild JA (1999). Site-directed mutagenesis of proline 204 in the 'hinge' region of yeast phosphoglycerate kinase. Eur J Biochem, 259(3), 939-945.

Abstract. Author URL.

Bourne PC, Isupov MN, Littlechild JA (1999). THE ATOMIC RESOLUTION (1.15 angstrom) STRUCTURE OF a NOVEL BACTERIAL ESTERASE. Author URL.

Schroder E, Isupov MI, Littlechild JA (1999). X-RAY STRUCTURAL STUDIES WITH HUMAN THIOREDOXIN PEROXIDASE. Author URL.

Isupov MN, Lebedev AA, Harutyunyan EH, Antson FA, Wilson KS, Dodson GG, Zakomirdina LN, Littlechild JA, Dementieva IS (1999). X-RAY STUDIES OF TRYPTOPHANASE. Author URL.

Crowhurst G, Isupov MN, Littlechild JA (1999). X-RAY STUDIES OF TWO GLYCOLYTIC ENZYMES FROM THE ARCHAEON SULFOLOBUS SOLFATARICUS. Author URL.

1998

Crowhurst GS, Isupov MN, Fleming T, Littlechild JA (1998). Two glycolytic enzymes from Sulfolobus solfataricus. Author URL.

1997

Yagnik AT, Littlechild JA, Turner NJ (1997). Molecular modelling studies of substrate binding to the lipase from Rhizomucor miehei. J Comput Aided Mol Des, 11(3), 256-264. Abstract. Author URL.

Bentley PA, Kroutil W, Littlechild JA, Roberts SM (1997). Preparation of polyamino acid catalysts for use in Julia asymmetric epoxidation. Chirality, 9(2), 198-202. Abstract.

1996

Dalby A, Rush C, Willetts A, Davies G, Dauter Z, Littlechild J (1996). ANALYSIS OF THE VANADIUM DEPENDENT HALOPEROXIDASE FROM CORALLINA OFFICINALIS. Author URL.

Dalby A, Rawas A, Watson HC, Littlechild JA (1996). Crystallisation and preliminary x-ray diffraction studies on human liver aldolase. Protein and Peptide Letters, 3(3), 207-212. Abstract.

Brabban AD, Littlechild J, Wisdom R (1996). Stereospecific γ-lactamase activity in a Pseudomonas fluorescens species. Journal of Industrial Microbiology, 16(1), 8-14. Abstract.

Dalby A, Littlechild JA (1996). Studies with type I aldolase to understand fructose intolerance and combat parasitic disease. J Pharm Pharmacol, 48(2), 214-217. Abstract. Author URL.

McGhie EJ, Littlechild JA (1996). The purification and crystallisation of 2,5-diketocamphane 1,2 monooxygenase and 3,6-diketocamphane 1,6 monooxygenase from Pseudomonas putida NCIMB 10007.

1995

1994

1993

Littlechild JA, Watson HC (1993). A data-based reaction mechanism for type I fructose bisphosphate aldolase. Trends Biochem Sci, 18(2), 36-39. Abstract. Author URL.

1992

Eisenberg D, Perutz MF, Buckingham AD, Graf L, Thornton J, Blow DM, Fersht AR, Karplus M, Johnson LN, Rippmann F, et al (1992). General discussion. Faraday Discussions, 93, 107-129.

Littlechild JA (1992). Structure and function. Nature, 359(6394), 448-449.

1991

Gamblin SJ, Davies GJ, Grimes JM, Jackson RM, Littlechild JA, Watson HC (1991). Activity and specificity of human aldolases. J Mol Biol, 219(4), 573-576. Abstract. Author URL.

Littlechild JA (1991). Protein crystallization: Magical or logical: can we establish some general rules?. Journal of Physics D: Applied Physics, 24(2), 111-118. Abstract.

1990

Watson HC, Littlechild JA (1990). Isoenzymes of phosphoglycerate kinase: evolutionary conservation of the structure of this glycolytic enzyme. Author URL.

1989

Abstract. Author URL.

1988

Wilson HR, Williams RJ, Littlechild JA, Watson HC (1988). NMR analysis of the interdomain region of yeast phosphoglycerate kinase. Eur J Biochem, 170(3), 529-538. Abstract. Author URL.

1987

1986

LITTLECHILD JA (1986). THE TYPE-II RESTRICTION ENZYMES HGIAI AND TAQI - PURIFICATION AND PROPERTIES. BIOCHEMICAL SOCIETY TRANSACTIONS, 14(2), 268-268. Author URL.

1984

1983

1982

Paterakis K, Littlechild J (1982). Structural domains of ribosomal protein S8 and their relationship to ribosomal RNA binding. FEBS Lett, 149(2), 328-333. Abstract. Author URL.

1981

Georgalis Y, Giri L, Littlechild JA (1981). Physical studies on the ribosomal protein S2 from the Escherichia coli 30S. Biochemistry, 20(5), 1061-1064. Abstract. Author URL.

Pawlik RT, Littlechild J, Pon C, Gualerzi C (1981). Purification and properties of Escherichia coli translational initiation factors. Biochemistry International, 2(4), 421-428.

1980

Littlechild J (1980). Proton magnetic resonance studies of Escherichia coli ribosomal protein S16. FEBS Lett, 111(1), 51-55. Author URL.

1979

Dijk J, Littlechild J (1979). Purification of ribosomal proteins from Escherichia coli under nondenaturing conditions. Methods Enzymol, 59, 481-502. Author URL.

1978

Österberg R, Sjöberg B, Littlechild J (1978). Small-angle X-ray scattering study of the proteins S1, S8, S15, S16, S20 from Escherichia coli ribosomes. FEBS Letters, 93(1), 115-119.

1977

Giri L, Littlechild J, Dijk J (1977). Hydrodynamic studies on the Escherichia coli robosomal proteins S8 and L6, prepared by two different methods. FEBS Lett, 79(2), 238-244. Author URL.

Österberg R, Sjöberg B, Garrett RA, Littlechild J (1977). Small-angle X-ray scattering study of the 16 S RNA binding protein S4 from Escherichia coli ribosomes. FEBS Letters, 73(1), 22-24.

Dijk J, Littlechild J, Garrett RA (1977). The RNA binding properties of "native" protein-protein complexes isolated from the Escherichia coli ribosome. FEBS Lett, 77(2), 295-300. Author URL.

Littlechild J, Dijk J, Garrett RA (1977). The identification of new RNA-binding proteins in the Escherichia coli ribosome. FEBS Lett, 74(2), 292-294. Author URL.

1973

Littlechild J, Spencer M (1973). Stability and homogeneity of preparations of ribosomal particles from Escherichia coli. Biochemistry, 12(16), 3102-3108. Author URL.

jenny_littlechild Details from cache as at 2023-09-26 07:59:08

Refresh publications

External Engagement and Impact

Committee/panel activities

Member of the Doctoral Training Centres Panel

Member of Advisory Committee MRC current

Member of Life Science Committee EPSRC current

Member of User Group 1 - Protein Crystallography current

Member of the Advisory Board - Journal of Molecular Recognition current

Evaluatuon committees EPSRC Doctoral Training Programmes 2013

Evaluation of BBSRC Industrial Biotechnology Networks 2013

Core Member of BBSRC Committee D 2010 onwards

UK representative and vice chair for European Section of Applied Biocatalysis 2007-onwards

Round Table Discussion Journal of Industrial Biotechnology 2007
‘Contributions of Marine Bioscience to Industrial Biotechnology’

Member of RSC Chemical/Biology Forum 2003-2006

Member of BBSRC BMS Committee 1995-1998

EU Activities

Contributed to writing of SusChem (Sustainable Chemistry for Europe) documentation 2006-2007

Attended European Section of Applied Biocatalyis meetings in Brussels, Germany, Austria 2007-2013

Evaluation of EU Framework 7 call on ‘Designer Enzymes’, 2009

Evaluation of major EU grants 2012 and 2013.Industrial Biocatalysis

Advisor to EU Commission on Biotechnology and Bioinformatics, Brussels,2009

Evaluation of applications for ERC grants, New Investigators 2009 onwards

EU commission advisory committee in Brussels on Industrial Biotechnology and evaluation of mid term large consortia grants 2012-2013.

UK member of COST Action CASCAT, SYSTEMS BIOCATALYSIS

Evaluation of ERC grants

Invited Article in European Reports in Biotechnology 2008 ‘Robust Enzyme Catalysts with Commercial Applications’

Member of INSTRUCT UK Liaison Group, for the Development of Central Facilities for Structural Biology in Europe.

Member of Biosciences for Business, KTN

Editorial responsibilities

Editorial Board International Journal Extremophiles. current

Editorial Board – Biotechnology Letters

Refereeing grant proposals UK, NIH, USA New Zealand, Norway and France

Refereeing papers for major international journals

Refereeing proposals for Queens Anniversary Awards 2006

Reviewing of Grants for MRC, BBSRC, EPSRC and Wellcome Trust, Innovate UK

Reviewing of scientific papers for high impact scientific journals

Review of major BBSRC and EPSRC Facilities, eg 2003 Chemical Database Service

Review of Queens Anniversary Awards

Member of BBSRC REI Committee 2004

Member of BBSRC Nibb Committee

Member of EPSRC Committees 2017

Member of BBSRC Equipment Committee 2018

Member of RSC Chemical/Biology Forum 2003 onwards

Member of Advisory Committee MRC

Member of the EPSRC/BBSRC Biomolecular Sciences Committee until 1998.

Member of Life Science Committee EPSRC current

Member of User Group 1 - Protein Crystallography, Daresbury laboratory

Member of the Advisory Board - Journal of Molecular Recognition.

Editorial Board International Journal Extremophiles

Invited lectures

American Chemical Society Meeting, San Francisco, USA August 2006

International Conference on Extremophiles, Brest, France Sep. 2006

International Meeting on Industrial Enzymes, Osaka, Japan March 2007

International Protein Stabilisation Conference, University of Exeter, April 2007

Max-Planck Symposium on Ribosomes, Berlin May 2007

International Meeting on Amino Acids and Proteins, Greece August 2007

EU Meeting on Industrial Biotechnology, Symbiosis, Barcelona, September 2007

International Meeting on Thermophiles, Bergen, September 2007

Invited lecture International Meeting on Vanadium Enzymes, Lisbon, Portugal, July 2008

International Conference on Extremophiles, Cape Town,South Africa, September 2008

International BIOPROSP 2009 Meeting, Tromso, Norway, February 2009

International ProStab Meeting, Graz, Austria, April 2009

International Biotrans 2009 Meeting, Bern, Switzerland July 2009

Keynote Lecture International Thermophiles 2009, Beijing, China, August 2009

Session Chair and Keynote Lecture European Symbiosis Meeting, Barcelona, Spain, September 2009.

Plenary Lecture South African Biochemical Society, Bloemfontaine, South Africa, Jan 2010

Invited lecture International Thermophiles Meeting, Montana, USA and International Extremophiles Meeting, Athens, Georgia, USA 9th -17th September 2011

Invited lecture International Extremophile Meeting – Key to Bioenergy Athens Geogia, USA Sep 19th -20th 2011

Invited lecture and session chair -International Marine Biodiversity Meeting, Aberdeen, Scotland26th -30th Sep 2011

International Biotransformation Conference, ESAB Meeting and COST Meeting, Naxos, Sicily.30th Sep to 8th Oct, 2011

Invited speaker - International Protein Stabilisation Meeting, Lisbon, Portugal, May 2nd-4th 2012.

Keynote speaker Leading Industrial Biotechnology. Focus on Biotechnology, York, UK May 2012

Invited lecture-International Extremophile Meeting, Seville, Spain, September 2012

Invited lecture and session chair International Conference on Marine Biotechnology, Dalian, China , September, 2012

Invited lecture -International Zing Conference on Biocatalysis, Cacun, Mexico December 2012

Invited lecture -International Transaminase Meeting, Stockholm, Sweden, Feb 2013

Keynote speaker-International Thermophile Meeting.Regensburg, Germany, September 2013

Recent Lectures

Invited lecture International Thermophiles Meeting, Montana, USA and International Extremophiles Meeting, USA September 2011

Invited lecture International Extremophile Meeting – Key to Bioenergy Athens Geogia, USA Sep 19th -20th 2011

Invited lecture and session chair -International Marine Biodiversity Meeting, Aberdeen, Scotland 26th -30th Sep 2011

International Biotransformation Conference, ESAB Meeting and COST Meeting, Naxos, Sicily.30th Sep to 8th Oct, 2011

Invited speaker International Protein Stabilisation Meeting, Lisbon, Portugal, May 2nd-4th 2012.

Keynote speaker Leading Industrial Biotechnology. Focus on Biotechnology, York, UK May 2012

Invited lecture-International Extremophile Meeting, Seville, Spain, September 2012

Invited lecture and session chair International Conference on Marine Biotechnology, Dalian, China , September, 2012

Invited lecture -International Zing Conference on Biocatalysis, Cacun, Mexico December 2012

Invited lecture -International Transaminase Meeting, Stockholm, Sweden, Feb 2013

Keynote speaker-International Thermophile Meeting, Regensburg, Germany, September 2013

Invited lecture International Extremophiles Meeting, St Petersburg, Russia, September, 2014

Invited lecture International Protein Stabilisation Meeting, Stressa, Italy, May 2014

Invited lecture International Novel Enzymes Meeting, Gent, Belgium, Oct. 2014

Invited lecture TRANSAM Meeting, Greitswald, Germany, Feb. 2015

Invited lecture International Biotrans Meeting, Vienna, July 2015

Invited Lecture US Society of Molecular Biology, Philidelphia, US, August 2015

Plenary Lecture International Thermophiles Meeting, Chile, September, 2015

Plenary Lecture 11th International Conference on Protein Stabilisation ProtStab, Istanbul, Turkey, 9th -11th May 2016

Invited Lecture 12th International Conference on Renewable Resources and Biorefineries , Ghent, Belgium 30th May – 1st June 2016

Plenary Lecture, European Congress on Biotechnology, ECIB16 Krakow, Poland, 3rd to 6th July 2016

Invited lecture, Ecc International Extremophile Meeting, Sophia, Bulgaria, September, 2016

Invited Lecture International Russian Biochemistry Meeting, Sochi, Russia 3rd-10th October 2016

Keynote Lecture International Thermophile Meeting, South Africa, 24th August to 1st Sep, 2017

Keynote Lecture International Biotechnology Meeting, March, London, 2018

Keynote Lecture International Protein Stabilisation Meeting, ProStab, Vilnius, Lithuania, May 2018

Keynote Lecture ECB18 ESAB/Asian Meeting, Geneva, July, 2018

7th International School on the Crystallography of Biological Macromolecules Como, Italy, May 2003

International Thermophile Meeting, Exeter, Sep. 2003

International Biocatalysis Meeting, Hamburg, Germany, Aug. 2004

International Vanadium Meeting, Budapest Hungary, 2004

RSC Frontiers Meeting in Mechanistic Enzymology and Biocatalysis, Exeter Aug-Sep. 2005

International Extremophile Meeting in Baltimore, USA Sep. 2004

US Biocatalysis Company, Diversa, USA Sep 2005

International Thermophiles 2005, Brisban, Australia, Sep. 2005

International Symposium on Extremophiles and Their Applications, Japan, Nov. 2005

International Symposium on Hydration in Proteins, Japan, Nov 2005

International Conference on Extremophiles, Brest, France, Sep. 2006

Coast to Coast Meeting on Medicinal Chemistry, Torquay, 2006

International Symposium on Vanadium, San Francisco, USA Sep. 2006

International Meeting on Industrial Enzymes, Osaka, Japan March, 2007

International Protein Stabilisation Conference, University of Exeter, April 2007

Max-Planck Symposium on Ribosomes, Berlin May 2007

International Meeting on Amino Acids and Proteins, Greece August 2007

International Meeting on Thermophiles, Bergen, Norway Sep. 2007

Pacific Rim Conference on Biotechnology, Hawaii, USA, Nov. 2007

South West Structural Biology Consortium 2002, 2003, 2004, 2005, 2006, 2007, 2008 (Exeter)

Media Coverage

Invited Article in European Reports in Biotechnology 2008 ‘Robust Enzyme Catalysts with Commercial Applications’

Nature's Catalysts and New Pharmaceuticals. Lecture to the Institute of Biology, Devon Section

Lectures to Exeter Discussion group and Exeter Womens Society, 2004.

Presented work as part of Astrazeneca Meeting, Bio-Business Success in South West England.

Presented work at Peninsula Medical School Academic evenings in Exeter and Plymouth.

Interview and video clip of my groups work appearing on local news BBC TV

Interview and article appearing in Express and Echo, local newspaper, 2003

Featured in 'Excellence in SW Book' published by SWRDA

Article in the 'Biochemist' on Cures from the Ends of the Earth, new pharmaceuticals from thermophilic enzymes.

Cafe Scientific Lecture, Exeter Phoenix May 2007

Article in Devon Life July 2007 Cures from the Ends of the Earth

Press Release of DTI Fasttrack Award with Aquapharm, Oban, 2007

Workshops/Conferences organised

International Thermophiles meeting 2003 Exeter

International Protein Stabilisation Meeting, 2007 Exeter

International Novel Enzymes Meeting 2010

RSC Mechanistic Enzymology Meeting 2005 Exeter

South west Structural Biology Meetings Exeter 2001 and 2008

Teaching

Programme Director: BSc Biological and Medicinal Chemistry

Programme Director: MSc Biocatalysis

Modules:

BIO1311 Microbiology and Biochemistry,
BIO1313 Introduction to the Biotechnology Industry,
BIO2059 Methods of Analysis of Macromolecules,
BIO3057 Pharmacology, Medicinal Chemistry and Medical Therapeutics,
BIOM503 Essentials in Molecular Biology,
BIOM504 Sequence Alignment and Structural Biology,
BIOM029 Advanced Biological Chemistry

Modules

2023/24

Information not currently available

Professor Jenny Littlechild

Supervision / Group

Postdoctoral researchers

Dr Rob Gibson
Dr Anne-Marie Hickey
Dr Michail Isupov
Dr Kirsty Line
Dr Carrie Rye

Postgraduate researchers

Joseph Bull
Simone De Rose
Kamal Hamidi-Nokhostin
Paul James
Matthew Martin
Nathan Menderin
Halina Novak
Emma Reid
Vahid Saneei
Christopher Sayers
Katalin Szabo (with PMS)
Rita Vaz
Simon Willies
Justyna Worek

Back | Edit Profile

Profile

Professor Jennifer Littlechild

Professor of Biological Chemistry

Overview

Qualifications

Career

Links

Research group links

Research

Research interests

Research projects

Research networks

Research grants

Links

Publications

Key publications

Abstract:Amino acid properties may be useful in predicting clinical outcome in patients with Kir6.2 neonatal diabetes.

Abstract:Crystal structure and substrate specificity of the thermophilic serine:pyruvate aminotransferase from Sulfolobus solfataricus

Abstract:A microreactor for the study of biotransformations by a cross-linked gamma-lactamase enzyme.

Abstract:The binding of haem and zinc in the 1.9 a X-ray structure of Escherichia coli bacterioferritin.

Abstract:Vanadium containing bromoperoxidase--insights into the enzymatic mechanism using X-ray crystallography.

Abstract:The Fasciola hepatica thioredoxin: High resolution structure reveals two oxidation states.

Publications by category

Books

Journal articles

Abstract:Biocatalysis as Key to Sustainable Industrial Chemistry.

Abstract:Biocatalysis as Key to Sustainable Industrial Chemistry.

Abstract:Complexity reduction and opportunities in the design, integration and intensification of biocatalytic processes for metabolite synthesis

Abstract:Preface to Special Issue on Biocatalysis as Key to Sustainable Industrial Chemistry.

Abstract:Biochemical and Structural Characterisation of a Novel D-Lyxose Isomerase from the Hyperthermophilic Archaeon Thermofilum sp.

Abstract:SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Abstract:Biosensors and Diagnostics for Fungal Detection

Abstract:The crystal structure of Arabidopsis BON1 provides insights into the copine protein family.

Abstract:Structural basis for the Target DNA recognition and binding by the MYB domain of phosphate starvation response 1.

Abstract:X-ray structure of Fasciola hepatica Sigma class glutathione transferase 1 reveals a disulfide bond to support stability in gastro-intestinal environment

Abstract:Discovering novel hydrolases from hot environments.

Abstract:New thermophilic α/β class epoxide hydrolases found in metagenomes from hot environments

Abstract:Structural characterization of geranylgeranyl pyrophosphate synthase GACE1337 from the hyperthermophilic archaeon Geoglobus acetivorans.

Abstract:The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase. Corrigendum.

Abstract:Comments to Article by Willetts A. et al. Microorganisms 2016, 4, 38.

Abstract:Diversity of bacteria and archaea from two shallow marine hydrothermal vents from Vulcano Island.

Abstract:Stabilization of a lipolytic enzyme for commercial application

Abstract:Discovery and Characterization of a Thermostable and Highly Halotolerant GH5 Cellulase from an Icelandic Hot Spring Isolate.

Abstract:Structural and biochemical characterisation of Archaeoglobus fulgidus esterase reveals a bound CoA molecule in the vicinity of the active site

Abstract:Archaeal Enzymes and Applications in Industrial Biocatalysts

Abstract:Discovery and characterization of thermophilic limonene-1,2-epoxide hydrolases from hot spring metagenomic libraries.

Abstract:Enzymes from Extreme Environments and Their Industrial Applications.

Abstract:Structural studies of a thermophilic esterase from a new Planctomycetes species, Thermogutta terrifontis.

Abstract:The Structure of a Novel Thermophilic Esterase from the Planctomycetes Species, Thermogutta terrifontis Reveals an Open Active Site Due to a Minimal 'Cap' Domain.

Abstract:The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase.

Abstract:Biochemical and structural characterisation of a haloalkane dehalogenase from a marine Rhodobacteraceae.

Abstract:Characterization of a phosphotriesterase-like lactonase from the hyperthermoacidophilic crenarchaeon Vulcanisaeta moutnovskia.

Abstract:Determination of protein-ligand interactions using differential scanning fluorimetry.

Abstract:The structure of a tetrameric α-carbonic anhydrase from Thermovibrio ammonificans reveals a core formed around intermolecular disulfides that contribute to its thermostability.

Abstract:The substrate specificity, enantioselectivity and structure of the (R)-selective amine : pyruvate transaminase from Nectria haematococca.

Abstract:Characterisation of an L-haloacid dehalogenase from the marine psychrophile Psychromonas ingrahamii with potential industrial application.

Abstract:Characterisation of an l-Haloacid Dehalogenase from the Marine Psychrophile Psychromonas ingrahamii with Potential Industrial Application

Abstract:Functional and structural characterisation of a viral cytochrome b5.

Abstract:Marine Rhodobacteraceae L-haloacid dehalogenase contains a novel His/Glu dyad that could activate the catalytic water.

Abstract:Marine enzymes with applications for biosynthesis of fine chemicals

Abstract:Protein structure and function

Abstract:Structural studies of Pseudomonas and Chromobacterium ω-aminotransferases provide insights into their differing substrate specificity.

Abstract:7.15 Oxidation: Haloperoxidases

Abstract:Amino acid properties may be useful in predicting clinical outcome in patients with Kir6.2 neonatal diabetes.

Abstract:Crystal structure and substrate specificity of the thermophilic serine:pyruvate aminotransferase from Sulfolobus solfataricus

Abstract:Coccolithophores: functional biodiversity, enzymes and bioprospecting.

Abstract:Thermophilic archaeal enzymes and applications in biocatalysis.

Abstract:An NADPH-dependent genetic switch regulates plant infection by the rice blast fungus.

Abstract:Crystal structure of a thermostable old yellow enzyme from Thermus scotoductus SA-01.

Abstract:Development of a high throughput screening tool for biotransformations utilising a thermophilic l-aminoacylase enzyme

Abstract:The development and evaluation of a conducting matrix for the electrochemical regeneration of the immobilised co-factor NAD(H) under continuous flow.

Abstract:Thermophilic enzymes and their applications in biocatalysis: a robust aldo-keto reductase.

Abstract:A microreactor for the study of biotransformations by a cross-linked gamma-lactamase enzyme.

Abstract:Biochemical and structural studies of a L-haloacid dehalogenase from the thermophilic archaeon Sulfolobus tokodaii.

Abstract:The binding of haem and zinc in the 1.9 a X-ray structure of Escherichia coli bacterioferritin.

Abstract:Vanadium containing bromoperoxidase--insights into the enzymatic mechanism using X-ray crystallography.

Abstract:Catalyst for improvement

Abstract:The Fasciola hepatica thioredoxin: High resolution structure reveals two oxidation states.

Abstract:An order-disorder twin crystal of L-2-haloacid dehalogenase from Sulfolobus tokodaii.

Abstract:Contributions of marine bioscience to industrial biotechology

Abstract:
Amino acid properties may be useful in predicting clinical outcome in patients with Kir6.2 neonatal diabetes.

Abstract:
Crystal structure and substrate specificity of the thermophilic serine:pyruvate aminotransferase from Sulfolobus solfataricus

Abstract:
A microreactor for the study of biotransformations by a cross-linked gamma-lactamase enzyme.

Abstract:
The binding of haem and zinc in the 1.9 a X-ray structure of Escherichia coli bacterioferritin.

Abstract:
Vanadium containing bromoperoxidase--insights into the enzymatic mechanism using X-ray crystallography.

Abstract:
The Fasciola hepatica thioredoxin: High resolution structure reveals two oxidation states.

Abstract:
Biocatalysis as Key to Sustainable Industrial Chemistry.

Abstract:
Biocatalysis as Key to Sustainable Industrial Chemistry.

Abstract:
Complexity reduction and opportunities in the design, integration and intensification of biocatalytic processes for metabolite synthesis

Abstract:
Preface to Special Issue on Biocatalysis as Key to Sustainable Industrial Chemistry.

Abstract:
Biochemical and Structural Characterisation of a Novel D-Lyxose Isomerase from the Hyperthermophilic Archaeon Thermofilum sp.

Abstract:
SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Abstract:
Biosensors and Diagnostics for Fungal Detection

Abstract:
The crystal structure of Arabidopsis BON1 provides insights into the copine protein family.

Abstract:
Structural basis for the Target DNA recognition and binding by the MYB domain of phosphate starvation response 1.

Abstract:
X-ray structure of Fasciola hepatica Sigma class glutathione transferase 1 reveals a disulfide bond to support stability in gastro-intestinal environment

Abstract:
Discovering novel hydrolases from hot environments.

Abstract:
New thermophilic α/β class epoxide hydrolases found in metagenomes from hot environments

Abstract:
Structural characterization of geranylgeranyl pyrophosphate synthase GACE1337 from the hyperthermophilic archaeon Geoglobus acetivorans.

Abstract:
The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase. Corrigendum.

Abstract:
Comments to Article by Willetts A. et al. Microorganisms 2016, 4, 38.

Abstract:
Diversity of bacteria and archaea from two shallow marine hydrothermal vents from Vulcano Island.

Abstract:
Stabilization of a lipolytic enzyme for commercial application

Abstract:
Discovery and Characterization of a Thermostable and Highly Halotolerant GH5 Cellulase from an Icelandic Hot Spring Isolate.

Abstract:
Structural and biochemical characterisation of Archaeoglobus fulgidus esterase reveals a bound CoA molecule in the vicinity of the active site

Abstract:
Archaeal Enzymes and Applications in Industrial Biocatalysts

Abstract:
Discovery and characterization of thermophilic limonene-1,2-epoxide hydrolases from hot spring metagenomic libraries.

Abstract:
Enzymes from Extreme Environments and Their Industrial Applications.

Abstract:
Structural studies of a thermophilic esterase from a new Planctomycetes species, Thermogutta terrifontis.

Abstract:
The Structure of a Novel Thermophilic Esterase from the Planctomycetes Species, Thermogutta terrifontis Reveals an Open Active Site Due to a Minimal 'Cap' Domain.

Abstract:
The oxygenating constituent of 3,6-diketocamphane monooxygenase from the CAM plasmid of Pseudomonas putida: the first crystal structure of a type II Baeyer-Villiger monooxygenase.

Abstract:
Biochemical and structural characterisation of a haloalkane dehalogenase from a marine Rhodobacteraceae.

Abstract:
Characterization of a phosphotriesterase-like lactonase from the hyperthermoacidophilic crenarchaeon Vulcanisaeta moutnovskia.

Abstract:
Determination of protein-ligand interactions using differential scanning fluorimetry.

Abstract:
The structure of a tetrameric α-carbonic anhydrase from Thermovibrio ammonificans reveals a core formed around intermolecular disulfides that contribute to its thermostability.

Abstract:
The substrate specificity, enantioselectivity and structure of the (R)-selective amine : pyruvate transaminase from Nectria haematococca.

Abstract:
Characterisation of an L-haloacid dehalogenase from the marine psychrophile Psychromonas ingrahamii with potential industrial application.

Abstract:
Characterisation of an l-Haloacid Dehalogenase from the Marine Psychrophile Psychromonas ingrahamii with Potential Industrial Application

Abstract:
Functional and structural characterisation of a viral cytochrome b5.

Abstract:
Marine Rhodobacteraceae L-haloacid dehalogenase contains a novel His/Glu dyad that could activate the catalytic water.

Abstract:
Marine enzymes with applications for biosynthesis of fine chemicals

Abstract:
Protein structure and function

Abstract:
Structural studies of Pseudomonas and Chromobacterium ω-aminotransferases provide insights into their differing substrate specificity.

Abstract:
7.15 Oxidation: Haloperoxidases

Abstract:
Amino acid properties may be useful in predicting clinical outcome in patients with Kir6.2 neonatal diabetes.

Abstract:
Crystal structure and substrate specificity of the thermophilic serine:pyruvate aminotransferase from Sulfolobus solfataricus

Abstract:
Coccolithophores: functional biodiversity, enzymes and bioprospecting.

Abstract:
Thermophilic archaeal enzymes and applications in biocatalysis.

Abstract:
An NADPH-dependent genetic switch regulates plant infection by the rice blast fungus.

Abstract:
Crystal structure of a thermostable old yellow enzyme from Thermus scotoductus SA-01.

Abstract:
Development of a high throughput screening tool for biotransformations utilising a thermophilic l-aminoacylase enzyme

Abstract:
The development and evaluation of a conducting matrix for the electrochemical regeneration of the immobilised co-factor NAD(H) under continuous flow.

Abstract:
Thermophilic enzymes and their applications in biocatalysis: a robust aldo-keto reductase.

Abstract:
A microreactor for the study of biotransformations by a cross-linked gamma-lactamase enzyme.

Abstract:
Biochemical and structural studies of a L-haloacid dehalogenase from the thermophilic archaeon Sulfolobus tokodaii.

Abstract:
The binding of haem and zinc in the 1.9 a X-ray structure of Escherichia coli bacterioferritin.

Abstract:
Vanadium containing bromoperoxidase--insights into the enzymatic mechanism using X-ray crystallography.

Abstract:
Catalyst for improvement

Abstract:
The Fasciola hepatica thioredoxin: High resolution structure reveals two oxidation states.

Abstract:
An order-disorder twin crystal of L-2-haloacid dehalogenase from Sulfolobus tokodaii.

Abstract:
Contributions of marine bioscience to industrial biotechology

Abstract:
Crystallization and preliminary X-ray diffraction analysis of omega-amino acid:pyruvate transaminase from Chromobacterium violaceum.

Abstract:
Immobilization of thermophilic enzymes in miniaturized flow reactors.

Abstract:
Natural methods of protein stabilization: thermostable biocatalysts.

Abstract:
The dodecameric vanadium-dependent haloperoxidase from the marine algae Corallina officinalis: cloning, expression, and refolding of the recombinant enzyme.

Abstract:
Anion binding tripodal receptors as structural models for the active site of vanadium haloperoxidases and acid phosphatases

Abstract:
Arabidopsis thaliana VTC4 encodes L-galactose-1-P phosphatase, a plant ascorbic acid biosynthetic enzyme.

Abstract:
Enhancing effect of calcium and vanadium ions on thermal stability of bromoperoxidase from Corallina pilulifera.

Abstract:
Nature's catalysts and their applications in the pharmaceutical industry

Abstract:
Synthesis and characterisation of a ligand that forms a stable tetrahedral intermediate in the active site of the Aureobacterium species (-) gamma-lactamase.

Abstract:
Characteristics of nearly dry enzymes in organic solvents: Implications for biocatalysis in the absence of water

Abstract:
Cloning and expression of cytosolic phosphoglycerate kinase from pea (Pisum sativum L.).

Abstract:
Crystallization and preliminary X-ray diffraction studies of a fungal hydrolase from Ophiostoma novo-ulmi.

Abstract:
Modification of halogen specificity of a vanadium-dependent bromoperoxidase.

Abstract:
Probing the role of water in protein conformation and function

Abstract:
The use of a thermostable signature amidase in the resolution of the bicyclic synthon (rac)-γ-lactam

Abstract:
What can we learn by studying enzymes in non-aqueous media?

Abstract:
Crystallization and preliminary X-ray diffraction studies of a novel alcohol dehydrogenase from the hyperthermophilic archaeon Aeropyrum pernix.

Abstract:
A method for screening Baeyer-Villiger monooxygenase activity against monocyclic ketones

Abstract:
A thermostable L-aminoacylase from Thermococcus litoralis: cloning, overexpression, characterization, and applications in biotransformations.