Dr Patrick Baker
Tel: 0114 222 2725
In my group we use X-ray crystallography to determine the atomic structure of biological macromolecules and thus to elucidate their structure/function relationships. We work closely with the other structural biology groups in Sheffield and have strong collaborations with numerous research groups across the world. Our research can be divided into three broad areas:
Structural biology, X-ray crystallography, structural genomics, substrate specificity
Research In Depth
Developing new antimicrobial targets - structural genomics.
Bacterial pathogens are becoming of increasing importance in health care due to the spread of multi-antibiotic resistant strains. In order to develop new treatment regimes for infectious diseases it is crucial to identify novel therapeutic targets. Essential gene products are ideal, as they are required for cellular viability. In a pilot structural genomics project on Bacillus subtilis, around 30 novel putative essential genes have been identified via functional genomics. Many of these are present in a wide range of bacterial pathogens. The structures of seven of these essential gene products have been determined, one of these is the protein Luxs, which is involved in the regulation of gene expression in response to changes in cell density, a process called quorum sensing. LuxS is thought to catalyze the degradation of S-ribosylhomocysteine to homocysteine and the autoinducer molecule 4,5-dihydroxy-2,3-pentadione. The structure of LuxS [Ruzheinikov et al (2001)] shows that it is a homodimer with an apparently novel fold based on an eight stranded beta barrel, flanked by six alpha helices. Each active site contains a zinc ion coordinated by the conserved residues His54, His58 and Cys126, and includes residues from both subunits. S-ribosylhomocysteine binds in a deep pocket with the ribose moiety adjacent to the enzyme bound zinc ion. Access to the active site appears to be restricted and possibly requires conformational changes in the protein involving the movement of residues 125-129 and those at the N terminus. The autoinducer-2 signaling pathway has been linked to aspects of bacterial virulence and pathogenicity. The structural data on LuxS will provide opportunities for targeting this enzyme for the rational design of new antibiotics.
Developing new antimicrobial targets - peptide deformylase
In collaboration with British Biotech (Vernalis) we have also been investigating peptide deformylase (PDF), an essential bacterial metalloenzyme, which deformylates the N-formylmethionine of newly synthesized polypeptides and represents a novel target for antimicrobial chemotherapy. The structure of this enzyme in complex with a potent inhibitor of the enzyme, BB-3497 has recently been determined [Clements, et al.] which shows that the inhibitor binds to the protein to mimic the natural peptidic substrate, with the addition of a bidentate metal chelating hydroxamide to coordinate the metal in the active site. BB-3947 has activity against both Gram-positive and Gram-negative bacteria and the mode of action is primarily bacteriostatic. It is rapidly and well absorbed following oral administration and is effective in a mouse systemic infection model with S. aureus, showing that PDF is a valid target for antimicrobial drug development.
Substrate specificity and chiral synthesis - the amino acid dehydrogenase family
The use of enzymes as biocatalysts to produce novel, chirally pure chemicals is of increasing industrial importance. Understanding how Nature has evolved different strategies for altering substrate specificity in families of enzymes is crucial in using site directed mutagenesis to produce mutant enzymes acting on novel compounds. Investigating the molecular basis of substrate specificity in the amino acid dehydrogenase family is one area of my research. Determination of the atomic structures of glutamate dehydrogenase, leucine dehydrogenase and phenylalanine dehydrogenase has shown that these three enzymes share the same three dimensional subunit structures, similar active sites, and identical residues involved in the catalytic chemistry. However, a combination of point mutations and subtle main chain movement, in the substrate side chain binding sites linked to the quaternary structure, account for the differential substrate specificity seen in this family of enzymes [Baker et al, Biochemistry (1997)]. A program of site-directed mutagenesis is now underway, with the object of producing mutant enzymes with novel specificities. These can be used for the production of chirally pure novel non-proteogenic amino acids for use in the pharmaceutical industry and also as diagnostic reagents for the detection of raised levels of amino acids in serum, crucial for the correct diagnosis of a number of genetic diseases of neonates such as phenylketonuria, homocysteinuria and maple syrup urine disease. We have succeeded in engineering a member of this enzyme family to have the ideal properties required in a spectrophotometric assay for phenylketonuria and the mutant is undergoing trials in the clinic [Wang et al (2001)].
Substrate specificity and chiral synthesis - methylaspartate ammonia lyase
Another enzyme that has biotechnological potential for the chiral synthesis of a number of novel amino acids is methylaspartate ammonia lyase (MAL), which catalyzes the magnesium-dependent reversible alpha-beta elimination of ammonia from L-threo-(2S,3S)-3-methylaspartic acid to mesaconic acid. The 1.3 Å crystal structure of the dimeric Citrobacter amalonaticus MAL has been determined using Seleno-methionine MAD experiments and shows that each subunit comprises two domains, one of which adopts the classical TIM barrel fold, with the active site at the C-terminal end of the barrel [Levy et al (2002)]. Despite very low sequence similarity, the structure of MAL is closely related to those of representative members of the enolase superfamily, indicating that the mechanism of MAL involves the initial abstraction of a proton to the 3-carboxyl of (2S,3S)-3-methylasparic acid to yield an enolic intermediate. This analysis resolves the conflict that had linked MAL to the histidine and phenylalanine ammonia lyase family of enzymes.
Substrate specificity and chiral synthesis - alanine dehydrogenase.
Alanine dehydrogenase (AlaDH) catalyses the NADH-dependent reversible reductive amination of pyruvate to L-alanine and is a key factor in the assimilation of L-alanine as an energy source through the tricarboxylic acid cycle during sporulation. The structure of alanine dehydrogenase from the cyanobacterium Phormidium lapideum and also from Bacillus stearothermophilus [Baker et al (1998)], shows that, despite catalyzing the same oxidative deamination reaction as the other amino acid dehydrogenases, AlaDH is structurally totally different, sharing the same fold as that of the D-2-hydroxyacid dehydrogenases and component dI of transhydrogenase.
Membrane bound ion pumps are involved in metabolic regulation, osmoregulation, cell signalling, nerve transmission and energy transduction. How the ion electrochemical gradient interacts with the scalar chemistry, and how the catalytic machinery is gated to ensure high coupling efficiency, are fundamental to the mechanism of action of such pumps. Transhydrogenase is a conformationally-coupled proton pump linking a proton gradient to the redox reaction between NAD(H) and NADP(H) and is important in the production of NADPH for the biosynthesis of amino acids and steroids, for detoxification, including limitation of the damage caused by free radicals and for the correct poising of the cellular electrochemical gradient. The enzyme has three components: dI binds NAD(H), dII spans the membrane and dIII binds NADP(H). Using seleno-methionine multiwavelength anomalous dispersion data collected at the ESRF synchrotron at Grenoble, with 52 selenium sites in the asymmetric unit, the structure of the dI component of this enzyme from Rhodospirulum rubrum [Buckley et al (2000)] has been successfully determined. This structure has revealed how the dI and dIII polypeptides may associate in the intact complex and explains the gating of the scalar hydride-tr ansfer reaction.
The molecular basis of extreme stability in proteins - glutamate dehydrogenase
As part of our research programme on amino acid dehydrogenases, we have determined the structure of glutamate dehydrogenase (GluDH) from Pyrococcus furiosus and Thermococcus litoralis -hyperthermophilic organisms with slightly different thermostabilities. These structures reveal that the formation of extended ion-pair networks is a major stabilizing feature in the adaptation of the organism to life at 100°C [Britton et al (1999)]. An extra ion-pair network has been engineered into the T. litoralis enzyme, increasing its thermostability [Vetriani et al (1998)]. The structure determination of other hyperthermophilic proteins, enzymes from psychrophilic sources and proteins from halophiles is now extending this work into understanding the molecular basis of thermostability, cold tolerance and the forces governing the adaptation of proteins to extremely high concentrations of salt.
The molecular basis of extreme stability in proteins - phosphoglucose isomerase.
We have determined the structure of the phosphoglucose isomerase (PGI) from Pyrococcus furiosus [Berrisford et al (2003)]. This PGI is a dimer of identical 23.5-kDa subunits and catalyzes the reversible isomerization of glucose 6-phosphate to fructose 6-phosphate. The structure has revealed that the fold of this enzyme is based on a cupin domain and is completely different to the alpha-beta-alpha sandwich of the much larger structure of the eukaryotic and bacterial PGIs. Despite these quite different architectures of the polypeptide backbones, the active site of both classes of PGI are remarkably similar, suggesting that they use similar reaction mechanisms. At its optimum temperature of 90°C, PF PGI has a half-life of 2.4 h. Analysis of the structure has shown, like in other thermostable enzymes, a number of ion pair interactions, which cluster into networks. We are currently investigating whether these networks are involved in the thermostability of this this enzyme.
Collaborating research groups.
Level 4 Modules
MBB403 Dissemination of Research Results
Level 3 Modules
MBB340 The Microbiology of Extreme Environments
Level 2 Modules
MBB261 Biochemistry 2 (Module coordinator)
Level 1 Modules
- Identification and structural analysis of the tripartite α-pore forming toxin of Aeromonas hydrophila. Nature Communications, 10(1). View this article in WRRO
- The molecular basis of endolytic activity of a multidomain alginate lyase from Defluviitalea phaphyphila, a representative of a new lyase family, PL39. Journal of Biological Chemistry, 294(48), 18077-18091.
- Distant non-obvious mutations influence the activity of a hyperthermophilic Pyrococcus furiosus phosphoglucose isomerase. Biomolecules, 9(6). View this article in WRRO
- Structural insights into the function of type VI secretion system TssA subunits.. Nature Communications, 9. View this article in WRRO
- TssA from Aeromonas hydrophila: Expression, purification and crystallographic studies. Acta Crystallographica Section F: Structural Biology Communications, 74(9), 578-582. View this article in WRRO
- TssA from Burkholderia cenocepacia: expression, purification, crystallization and crystallographic analysis. Acta Crystallographica Section F Structural Biology Communications, 74(9), 536-542. View this article in WRRO
- Elucidating the structural basis for differing enzyme inhibitor potency by cryo-EM. Proceedings of the National Academy of Sciences of the United States of America, 115(8), 1795-1800. View this article in WRRO
- The molecular basis of phosphite and hypophosphite recognition by ABC-transporters. Nature Communications, 8(1). View this article in WRRO
- Pnc1 piggy-back import into peroxisomes relies on Gpd1 homodimerisation.. Scientific Reports, 7. View this article in WRRO
- Conserved Residues in Ycf54 are required for Protochlorophyllide Formation in Synechocystis sp. PCC 6803. Biochemical Journal. View this article in WRRO
- The mechanism of a formaldehyde-sensing transcriptional regulator.. Scientific Reports, 6. View this article in WRRO
- Mirror-Image Packing Provides a Molecular Basis for the Nanomolar Equipotency of Enantiomers of an Experimental Herbicide. Angewandte Chemie International Edition, 55(43), 13485-13489. View this article in WRRO
- Mirror-Image Packing Provides a Molecular Basis for the Nanomolar Equipotency of Enantiomers of an Experimental Herbicide. Angewandte Chemie, 128(43), 13683-13687. View this article in WRRO
- Crystal Structures Reveal that the Reaction Mechanism of Imidazoleglycerol-Phosphate Dehydratase Is Controlled by Switching Mn(II) Coordination. Structure, 23(7), 1236-1245. View this article in WRRO
- Columnar Liquid Crystals in Cylindrical Nanoconfinement. ACS Nano, 9(2), 1759-1766. View this article in WRRO
- Crystallization and preliminary crystallographic analysis of the putative sugar-binding protein Msmeg_0515 (AgaE) fromMycobacterium smegmatis. Acta Crystallographica Section F Structural Biology Communications, 71(2), 189-193.
- Study of zinc protein ligands in a halophilic enzyme. Current Topics in Peptide and Protein Research, 15, 91-98.
- Crystallization and preliminary crystallographic analysis of a surface antigen glycoprotein, SAG19, from Eimeria tenella.. Acta Crystallogr Sect F Struct Biol Cryst Commun, 69(Pt 12), 1380-1383.
- Crystallization and preliminary X-ray analysis of the receiver domain of a putative response regulator, BPSL0128, from Burkholderia pseudomallei.. Acta Crystallogr Sect F Struct Biol Cryst Commun, 68(Pt 8), 917-922.
- Cloning, purification, crystallization and preliminary X-ray analysis of the Burkholderia pseudomallei L1 ribosomal protein.. Acta Crystallogr Sect F Struct Biol Cryst Commun, 68(Pt 3), 347-350.
- Cloning, purification and crystallographic analysis of a hypothetical protein, BPSL1549, from Burkholderia pseudomallei.. Acta Crystallogr Sect F Struct Biol Cryst Commun, 67(Pt 12), 1623-1626.
- A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A.. Science, 334(6057), 821-824. View this article in WRRO
- Structural origins of pH-dependent chemical shifts in the B1 domain of protein G.. Proteins, 78(14), 3000-3016.
- Crystallization and preliminary X-ray analysis of D-2-hydroxyacid dehydrogenase from Haloferax mediterranei.. Acta Crystallogr Sect F Struct Biol Cryst Commun, 65(Pt 4), 415-418.
- Active site dynamics in the zinc-dependent medium chain alcohol dehydrogenase superfamily.. Proc Natl Acad Sci U S A, 106(3), 779-784.
- An inhibitor of FtsZ with potent and selective anti-staphylococcal activity.. Science, 321(5896), 1673-1675.
- Molecular basis for inhibition and resistance of glutamate racemase to a family of D-glu analogues. Acta Crystallographica Section A Foundations of Crystallography, 64(a1), C349-C349.
- Cloning, purification and preliminary crystallographic analysis of a putative DNA-binding membrane protein, YmfM, from Staphylococcus aureus.. Acta Crystallogr Sect F Struct Biol Cryst Commun, 64(Pt 7), 656-658.
- Crystal structure of S. aureus YlaN, an essential leucine rich protein involved in the control of cell shape.. Proteins, 68(2), 438-445.
- RusA Holliday junction resolvase: DNA complex structure--insights into selectivity and specificity.. Nucleic Acids Res, 34(19), 5577-5584. View this article in WRRO
- Cloning, purification and preliminary crystallographic analysis of a conserved hypothetical protein, SA0961 (YlaN), from Staphylococcus aureus.. Acta Crystallogr Sect F Struct Biol Cryst Commun, 62(Pt 8), 778-780. View this article in WRRO
- Evidence supporting a cis-enediol-based mechanism for Pyrococcus furiosus phosphoglucose isomerase.. J Mol Biol, 358(5), 1353-1366.
- Analysis of protein solvent interactions in glucose dehydrogenase from the extreme halophile Haloferax mediterranei.. Proc Natl Acad Sci U S A, 103(13), 4846-4851.
- Structure and mechanism of imidazoleglycerol-phosphate dehydratase.. Structure, 13(12), 1809-1817.
- Substrate-induced conformational changes in Bacillus subtilis glutamate racemase and their implications for drug discovery.. Structure, 13(11), 1707-1713.
- Crystallization and preliminary X-ray analysis of binary and ternary complexes of Haloferax mediterranei glucose dehydrogenase. ACTA CRYSTALLOGR F, 61, 743-746.
- Purification, crystallization and preliminary crystallographic analysis of Arabidopsis thaliana imidazoleglycerol-phosphate dehydratase.. Acta Crystallogr Sect F Struct Biol Cryst Commun, 61(Pt 8), 776-778.
- Expression, purification and preliminary X-ray analysis of crystals of Bacillus subtilis glutamate racemase.. Acta Crystallogr D Biol Crystallogr, 60(Pt 11), 2031-2034.
- The structures of inhibitor complexes of Pyrococcus furiosus phosphoglucose isomerase provide insights into substrate binding and catalysis.. J Mol Biol, 343(3), 649-657.
- Analysis of the open and closed conformations of the GTP-binding protein YsxC from Bacillus subtilis.. J Mol Biol, 339(2), 265-278.
- From hyperthermophiles to psychrophiles: the structural basis of temperature stability of the amino acid dehydrogenases.. Biochem Soc Trans, 32(Pt 2), 264-268.
- Substrate specificity and mechanism from the structure of Pyrococcus furiosus galactokinase.. J Mol Biol, 337(2), 387-398.
- Expression, purification, crystallization and preliminary crystallographic analysis of a putative GTP-binding protein, YsxC, from Bacillus subtilis.. Acta Crystallogr D Biol Crystallogr, 60(Pt 1), 166-168.
- The structure of Escherichia coli RusA endonuclease reveals a new Holliday junction DNA binding fold.. Structure, 11(12), 1557-1567.
- Optimization of selenium substructures as obtained from SHELXD. ACTA CRYSTALLOGR D, 59, 1987-1994.
- Purification, crystallization and preliminary crystallographic analysis of phosphoglucose isomerase from the hyperthermophilic archaeon Pyrococcus furiosus.. Acta Crystallogr D Biol Crystallogr, 59(Pt 10), 1822-1823.
- Cloning, purification, crystallization and preliminary crystallographic analysis of galactokinase from Pyrococcus furiosus.. Acta Crystallogr D Biol Crystallogr, 59(Pt 10), 1819-1821.
- Crystal structure of Pyrococcus furiosus phosphoglucose isomerase. Implications for substrate binding and catalysis.. J Biol Chem, 278(35), 33290-33297.
- The human granulocyte/macrophage colony-stimulating factor receptor α2 isoform influences haemopoietic lineage commitment and divergence. British Journal of Haematology, 122(1), 150-158.
- Alanine dehydrogenase from the psychrophilic bacterium strain PA-43: overexpression, molecular characterization, and sequence analysis. EXTREMOPHILES, 7(2), 135-143.
- Crystallization and preliminary X-ray analysis of the ytxM gene product from Bacillus subtilis.. Acta Crystallogr D Biol Crystallogr, 58(Pt 12), 2138-2140.
- Crystallization and preliminary X-ray crystallographic studies on the class II cholesterol oxidase from Burkholderia cepacia containing bound flavin.. Acta Crystallogr D Biol Crystallogr, 58(Pt 12), 2182-2183.
- X-ray crystallographic studies on butyryl-ACP reveal flexibility of the structure around a putative acyl chain binding site.. Structure, 10(6), 825-835.
- Crystallization and preliminary X-ray analysis of substrate complexes of leucine dehydrogenase from Thermoactinomyces intermedius.. Acta Crystallogr D Biol Crystallogr, 58(Pt 6 Pt 2), 1059-1062.
- The crystal structure of diadenosine tetraphosphate hydrolase from Caenorhabditis elegans in free and binary complex forms.. Structure, 10(4), 589-600.
- Crystallization and preliminary X-ray crystallographic studies on acyl-(acyl carrier protein) from Escherichia coli.. Acta Crystallogr D Biol Crystallogr, 58(Pt 2), 330-332.
- Insights into enzyme evolution revealed by the structure of methylaspartate ammonia lyase.. Structure, 10(1), 105-113.
- Crystallization and preliminary X-ray analysis of glucose dehydrogenase from Haloferax mediterranei.. Acta Crystallogr D Biol Crystallogr, 57(Pt 12), 1887-1889.
- Crystallization and preliminary X-ray analysis of Citrobacter amalonaticus methylaspartate ammonia lyase.. Acta Crystallogr D Biol Crystallogr, 57(Pt 12), 1922-1924.
- The 1.2 A structure of a novel quorum-sensing protein, Bacillus subtilis LuxS.. J Mol Biol, 313(1), 111-122.
- The crystal structure of Thermotoga maritima maltosyltransferase and its implications for the molecular basis of the novel transfer specificity.. J Mol Biol, 312(1), 119-131.
- The structure and domain organization of Escherichia coli isocitrate lyase.. Acta Crystallogr D Biol Crystallogr, 57(Pt 9), 1209-1218.
- Cloning, purification, crystallization and preliminary crystallographic analysis of Bacillus subtilis LuxS.. Acta Crystallogr D Biol Crystallogr, 57(Pt 9), 1324-1325.
- Glycerol dehydrogenase. structure, specificity, and mechanism of a family III polyol dehydrogenase.. Structure, 9(9), 789-802.
- Antibiotic activity and characterization of BB-3497, a novel peptide deformylase inhibitor. ANTIMICROB AGENTS CH, 45(2), 563-570.
- Purification, crystallization and quaternary structure analysis of a glycerol dehydrogenase S305C mutant from Bacillus stearothermophilus.. Acta Crystallogr D Biol Crystallogr, 57(Pt 1), 165-167.
- The mechanism of the oxidation of glycerol to dihydroxyacetone in Bacillus stearothermophilus. Biochemical Society Transactions, 28(5), A331-A331.
- Crystallization of the dI component of transhydrogenase, a proton-translocating membrane protein.. Acta Crystallogr D Biol Crystallogr, 56(Pt 9), 1170-1172.
- Protein-protein recognition, hydride transfer and proton pumping in the transhydrogenase complex.. Structure, 8(8), 809-815.
- Crystallization and preliminary X-ray crystallographic studies on maltosyltransferase from Thermotoga maritima.. Acta Crystallogr D Biol Crystallogr, 56(Pt 8), 1049-1050.
- The crystal structure and active site location of isocitrate lyase from the fungus Aspergillus nidulans.. Structure, 8(4), 349-362.
- Crystallographic analysis of triclosan bound to enoyl reductase.. J Mol Biol, 294(2), 527-535.
- Structure determination of the glutamate dehydrogenase from the hyperthermophile Thermococcus litoralis and its comparison with that from Pyrococcus furiosus.. J Mol Biol, 293(5), 1121-1132.
- Molecular basis of triclosan activity. NATURE, 398(6726), 383-384.
- Insights into the mechanism of domain closure and substrate specificity of glutamate dehydrogenase from Clostridium symbiosum.. J Mol Biol, 285(2), 875-885.
- Analysis of the structure and substrate binding of Phormidium lapideum alanine dehydrogenase.. Nat Struct Biol, 5(7), 561-567.
- Crystallization of the alanine dehydrogenase from Phormidium lapideum.. Acta Crystallogr D Biol Crystallogr, 54(Pt 3), 407-408.
- Crystallization of NAD+-dependent phenylalanine dehydrogenase from Nocardia sp239.. Acta Crystallogr D Biol Crystallogr, 54(Pt 2), 269-272.
- Determinants of substrate specificity in the superfamily of amino acid dehydrogenases.. Biochemistry, 36(51), 16109-16115.
- Analysis of the quaternary structure, substrate specificity, and catalytic mechanism of valine dehydrogenase.. J Biol Chem, 272(40), 25105-25111.
- Isocitrate lyase from Aspergillus nidulans: crystallization and X-ray analysis of a glyoxylate cycle enzyme.. Acta Crystallogr D Biol Crystallogr, 53(Pt 4), 488-490.
- Crystallization and preliminary X-ray studies of nitrogenase component 1 (the MoFe protein) from Klebsiella pneumoniae. Acta Crystallographica Section D Biological Crystallography, 53(2), 227-228.
- A mechanism of drug action revealed by structural studies of enoyl reductase.. Science, 274(5295), 2107-2110.
- Crystal structure of DNA recombination protein RuvA and a model for its binding to the Holliday junction.. Science, 274(5286), 415-421.
- The structure of Pyrococcus furiosus glutamate dehydrogenase reveals a key role for ion-pair networks in maintaining enzyme stability at extreme temperatures.. Structure, 3(11), 1147-1158.
- Common themes in redox chemistry emerge from the X-ray structure of oilseed rape (Brassica napus) enoyl acyl carrier protein reductase.. Structure, 3(9), 927-938.
- Purification and Crystallization of the Light Harvesting LH1 complex fromRhodobacter sphaeroides. Journal of Molecular Biology, 252(1), 153-153.
- Crystallization of glycerol dehydrogenase from Bacillus stearothermophilus.. Acta Crystallogr D Biol Crystallogr, 51(Pt 5), 830-832.
- Crystallization and analysis of the subunit assembly and quaternary structure of imidazoleglycerol phosphate dehydratase from Saccharomyces cerevisiae.. Acta Crystallogr D Biol Crystallogr, 51(Pt 5), 845-847.
- ALTERATION IN RELATIVE ACTIVITIES OF PHENYLALANINE DEHYDROGENASE TOWARDS DIFFERENT SUBSTRATES BY SITE-DIRECTED MUTAGENESIS. FEBS LETT, 370(1-2), 93-96.
- A role for quaternary structure in the substrate specificity of leucine dehydrogenase.. Structure, 3(7), 693-705.
- Insights into thermal stability from a comparison of the glutamate dehydrogenases from Pyrococcus furiosus and Thermococcus litoralis.. Eur J Biochem, 229(3), 688-695.
- Correlation of intron-exon organisation with the three-dimensional structure in glutamate dehydrogenase.. Biochim Biophys Acta, 1247(2), 231-238.
- Crystallization of the NAD(P)-dependent glutamate dehydrogenase from the hyperthermophile Pyrococcus furiosus.. Acta Crystallogr D Biol Crystallogr, 51(Pt 2), 240-242.
- Alteration of the amino acid substrate specificity of clostridial glutamate dehydrogenase by site-directed mutagenesis of an active-site lysine residue.. Protein Eng, 8(2), 147-152.
- Crystallization and preliminary X-ray studies of recombinant horseradish peroxidase. Acta Crystallographica Section D Biological Crystallography, 51(1), 121-123.
- The changed pattern of substrate specificity in the K89L mutant of glutamate dehydrogenase of Clostridium symbiosum.. Biochem Soc Trans, 22(3), 320S.
- The catalytic role of aspartate in the active site of glutamate dehydrogenase.. Biochem J, 301 ( Pt 1), 13-16.
- Crystallization and quaternary structure analysis of the NAD(+)-dependent leucine dehydrogenase from Bacillus sphaericus.. J Mol Biol, 236(2), 663-665.
- CRYSTALLIZATION OF THE NADP+-DEPENDENT GLUTAMATE-DEHYDROGENASE FROM ESCHERICHIA-COLI. J MOL BIOL, 234(4), 1270-1273.
- Conformational flexibility in glutamate dehydrogenase. Role of water in substrate recognition and catalysis.. J Mol Biol, 234(4), 1131-1139.
- Evolution of substrate diversity in the superfamily of amino acid dehydrogenases. Prospects for rational chiral synthesis.. J Mol Biol, 234(4), 938-945.
- STRUCTURAL CONSEQUENCES OF SEQUENCE PATTERNS IN THE FINGERPRINT REGION OF THE NUCLEOTIDE-BINDING FOLD (VOL 228, PG 662, 1992). JOURNAL OF MOLECULAR BIOLOGY, 232(3), 1012-1012.
- Erratum: Structural consequences of sequence patterns in the fingerprint region of the nucleotide binding fold (J. Mol. Biol. (1992) 228, 662-671). Journal of Molecular Biology, 232(3), 1012.
- Purification and crystallization of the light harvesting LH1 complex from Rhodobacter sphaeroides.. J Mol Biol, 228(4), 1259-1262.
- Structural consequences of sequence patterns in the fingerprint region of the nucleotide binding fold. Implications for nucleotide specificity.. J Mol Biol, 228(2), 662-671.
- Structural relationship between the hexameric and tetrameric family of glutamate dehydrogenases.. Eur J Biochem, 209(3), 851-859.
- Effect of additives on the crystallization of glutamate dehydrogenase from Clostridium symbiosum. Evidence for a ligand-induced conformational change.. J Mol Biol, 224(4), 1181-1184.
- Subunit assembly and active site location in the structure of glutamate dehydrogenase.. Proteins, 12(1), 75-86.
- The partial amino acid sequence of the NAD(+)-dependent glutamate dehydrogenase of Clostridium symbiosum: implications for the evolution and structural basis of coenzyme specificity.. Biochim Biophys Acta, 1080(3), 191-197.
- Use of chemical modification in the crystallization of isocitrate lyase from Escherichia coli.. J Mol Biol, 220(1), 13-16.
- ISOMORPHOUS REPLACEMENT WITH OPTIMIZED ANOMALOUS SCATTERING APPLIED TO PROTEIN CRYSTALLOGRAPHY. ACTA CRYSTALLOGR A, 46, 721-725.
- Recent progress on the structure and function of glutamate dehydrogenase.. Biochem Soc Trans, 15(4), 748-751.
- INTERPRETATION OF THE 2.5 A RESOLUTION CRYSTAL-STRUCTURE OF GDH. PROTEIN ENG, 1(3), 248-248.
- The crystal structure of glutamate dehydrogenase from Clostridium symbiosum at 0.6 nm resolution.. Biochem J, 242(3), 789-795.
- CRYSTALLIZATION OF AN NADP+-DEPENDENT MALIC ENZYME FROM RAT-LIVER. J MOL BIOL, 193(1), 233-235.
- Structural and functional studies of histidine biosynthesis in Acanthamoeba spp. demonstrates a novel molecular arrangement and target for antimicrobials. PLOS ONE, 13(7), e0198827-e0198827. View this article in WRRO
- Determination of the X-Ray Crystallographic Structure of E.coli Butyryl-ACP, Advanced Research on Plant Lipids (pp. 139-142). Springer Netherlands
- Imidazoleglycerol-Phosphate Dehydratase (IGPD) (pp. 1-13). John Wiley & Sons, Ltd
Conference proceedings papers
- Structure and Function of Amino Acid Ammonia-lyases. Biocatalysis and Biotransformation, Vol. 22(2) (pp 133-140)
- Crystal structure and mutational analysis of the diadenosine tetraphosphate (Ap4A) 'Nudix' hydrolase from Caenorhabditis elegans. DRUG DEVELOPMENT RESEARCH, Vol. 56(4) (pp 567-567)
- The Crystallization and structure analysis of the dI Component of Transhydrogenase, a Proton-Translocating Membrane Protein. Acta Crystallographica Section A Foundations of Crystallography, Vol. 56(s1) (pp s270-s270)
- Improving the engineered activity of mutants of clostridial glutamate dehydrogenase towards monocarboxylic substrates: Substitution of Ala163 with glycine. BIOCHEMICAL SOCIETY TRANSACTIONS, Vol. 24(1) (pp S126-S126)