Research Topics
| David LeysSummaryAffiliation: University of Leicester Country: UK Publications
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Detail Information
Publications
Probing the dynamic interface between trimethylamine dehydrogenase (TMADH) and electron transferring flavoprotein (ETF) in the TMADH-2ETF complex: role of the Arg-alpha237 (ETF) and Tyr-442 (TMADH) residue pairSelena G Burgess
Department of Biochemistry, University of Leicester, Leicester LE1 9HN, UK
Biochemistry 47:5168-81. 2008..Our work also points to the importance of Arg-alpha237 in controlling the thermodynamics of electron transfer, the dynamics of ETF, and the protection of reducing equivalents following disassembly of the TMADH-2ETF complex...
Channelling and formation of 'active' formaldehyde in dimethylglycine oxidaseDavid Leys
University of Leicester, Department of Biochemistry, University Road, Leicester LE1 7RH, UK
EMBO J 22:4038-48. 2003..This mode of channelling in DMGO is distinct from other channelling mechanisms...
Crystal structures at atomic resolution reveal the novel concept of "electron-harvesting" as a role for the small tetraheme cytochrome cDavid Leys
Laboratory of Protein Biochemistry and Protein Engineering, Department of Biochemistry, Physiology, and Microbiology, K L Ledeganckstraat 35, 9000 Gent, Belgium
J Biol Chem 277:35703-11. 2002..quot; This optimizes the efficiency of intermolecular electron transfer by maximizing chances of productive collision with redox partners...- Extensive conformational sampling in a ternary electron transfer complexDavid Leys
Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, UK
Nat Struct Biol 10:219-25. 2003..This study establishes the role of conformational sampling in multi-domain redox systems, providing insight into electron transfer between ETFs and structurally distinct redox partners... - Atomic structure of Mycobacterium tuberculosis CYP121 to 1.06 A reveals novel features of cytochrome P450David Leys
Department of Biochemistry, University of Leicester, The Adrian Building, University Road, Leicester LE1 7RH, United Kingdom
J Biol Chem 278:5141-7. 2003..Most interestingly, the electron density indicates weak binding of a dioxygen molecule to the P450. This structure provides a basis for rational design of putative antimycobacterial agents... - Crystal structure of the Mycobacterium tuberculosis P450 CYP121-fluconazole complex reveals new azole drug-P450 binding modeHarriet E Seward
Department of Biochemistry, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE6 0HQ, United Kingdom
J Biol Chem 281:39437-43. 2006.... - Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoproteinHelen S Toogood
Department of Biochemistry, University of Leicester, Henry Wellcome Building, Lancaster Road, LE1 7RH, Leicester United Kingdom
J Biol Chem 280:30361-6. 2005..ETF Glu-165beta plays a key role in stabilizing positions incompatible with fast interprotein electron transfer, thus ensuring high rates of complex dissociation... - Flavocytochrome P450 BM3 mutant A264E undergoes substrate-dependent formation of a novel heme iron ligand setHazel M Girvan
Department of Biochemistry, University of Leicester, Leicester LE1 7RH, United Kingdom
J Biol Chem 279:23274-86. 2004..Glutamate coordination of the heme iron is confirmed by structural studies of the A264E mutant (Joyce, M. G., Girvan, H. M., Munro, A. W., and Leys, D. (2004) J. Biol. Chem. 279, 23287-23293)... - Mechanism of FAD reduction and role of active site residues His-225 and Tyr-259 in Arthrobacter globiformis dimethylglycine oxidase: analysis of mutant structure and catalytic functionJaswir Basran
Department of Biochemistry, University of Leicester, UK
Biochemistry 45:11151-61. 2006..Our data are discussed in the context of the crystallographic data for DMGO and also in relation to contemporary mechanisms for flavoprotein-catalyzed oxidation of amine substrates... - Thermodynamic and biophysical characterization of cytochrome P450 BioI from Bacillus subtilisRachel J Lawson
Department of Biochemistry, University of Leicester, UK
Biochemistry 43:12410-26. 2004..Calorimetry shows that structural stability of the protein was altered by addition of the reductant dithiothreitol, suggesting that the disulfide is important to integrity of BioI structure... - Proton transfer in the oxidative half-reaction of pentaerythritol tetranitrate reductase. Structure of the reduced enzyme-progesterone complex and the roles of residues Tyr186, His181, His184Huma Khan
Department of Biochemistry, University of Leicester, UK
FEBS J 272:4660-71. 2005..Our data highlight mechanistic differences between Old Yellow Enzyme and PETN reductase and indicate that catalysis requires a metastable enzyme-steroid complex and not the most stable complex observed in crystallographic studies... - Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complexHelen S Toogood
Department of Biochemistry, University of Leicester, Leicester LE1 7RH, United Kingdom
J Biol Chem 279:32904-12. 2004.... - Expression, purification and spectroscopic characterization of the cytochrome P450 CYP121 from Mycobacterium tuberculosisKirsty J McLean
Department of Biochemistry, The Adrian Building, University of Leicester, UK
J Inorg Biochem 91:527-41. 2002..CYP121 binds very tightly to a range of azole antifungal drugs (e.g. clotrimazole, miconazole), suggesting that it may represent a novel target for these antibiotics in the M. tuberculosis pathogen... - The 1.25 A resolution structure of the diheme NapB subunit of soluble nitrate reductase reveals a novel cytochrome c fold with a stacked heme arrangementAnn Brigé
Laboratory of Protein Biochemistry and Protein Engineering, State University of Gent, Ledeganckstraat 35, B 9000 Gent, Belgium
Biochemistry 41:4827-36. 2002.... - A single mutation in cytochrome P450 BM3 induces the conformational rearrangement seen upon substrate binding in the wild-type enzymeM Gordon Joyce
Department of Biochemistry, University of Leicester, Leicester LE1 7RH, United Kingdom
J Biol Chem 279:23287-93. 2004.... - The crystal structure of the FAD/NADPH-binding domain of flavocytochrome P450 BM3Michael G Joyce
Department of Biochemistry, University of Leicester, Leicester, UK
FEBS J 279:1694-706. 2012..The FAD domain crystal structure enables molecular modelling of its interactions with its cognate FMN (flavodoxin-like) domain within the BM3 reductase module... - Electrical circuitry in biology: emerging principles from protein structureDavid Leys
Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, UK
Curr Opin Struct Biol 14:642-7. 2004..The use of an array of solvent-exposed, closely spaced redox centres can maximise productive collisions. Also, the use of conformational sampling via domain motion within the electron transfer complex optimises tunnelling probability... - Crystallization and preliminary X-ray diffraction analysis of a flavoenzyme amine dehydrogenase/oxidase from Pyrococcus furiosus DSM 3638Phillip J Monaghan
Department of Biochemistry, University of Leicester, Leicester LE1 7RH, England
Acta Crystallograph Sect F Struct Biol Cryst Commun 61:756-8. 2005..3, b = 136.3, c = 203.8 A, alpha = 94.5, beta = 99.4, gamma = 102.7 degrees and a = 93.7, b = 116.3, c = 126.9 A, alpha = 97.3, beta = 99.9, gamma = 104.6 degrees... - Crystallization and preliminary X-ray diffraction analysis of cytochrome c peroxidase from the purple phototrophic bacterium Rhodobacter capsulatusLina De Smet
Department of Biochemistry, Physiology and Microbiology, Laboratory for Protein Biochemistry and Protein Engineering, University of Gent, 9000 Gent, Belgium
Acta Crystallogr D Biol Crystallogr 58:522-3. 2002..2, b = 134.4, c = 167.9 A. These crystals diffracted to 2.7 A resolution and contained four peroxidase molecules per crystallographic asymmetric unit... - Trp(359) regulates flavin thermodynamics and coenzyme selectivity in Mycobacterium tuberculosis FprARajasekhar Neeli
Manchester Interdisciplinary Biocentre, The University of Manchester, Faculty of Life Sciences, 131 Princess Street, Manchester M1 7DN, UK
Biochem J 411:563-70. 2008..The results demonstrate that the conserved Trp(359) is critical in regulating FprA FAD binding, thermodynamic properties, catalytic efficiency and coenzyme selectivity... - Dynamics driving function: new insights from electron transferring flavoproteins and partner complexesHelen S Toogood
Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, Manchester, UK
FEBS J 274:5481-504. 2007..ETF complexes point to mechanisms of electron transfer in which 'dynamics drive function', a feature that is probably widespread in biology given the modular assembly and flexible nature of biological electron transfer systems... - Mechanism of coenzyme binding to human methionine synthase reductase revealed through the crystal structure of the FNR-like module and isothermal titration calorimetryKirsten R Wolthers
Faculty of Life Sciences, University of Manchester, Manchester Interdisciplinary Biocentre, 131 Princess Street, Manchester M1 7DN, United Kingdom
Biochemistry 46:11833-44. 2007..The biological implications of an attenuated mechanism of MS reactivation by MSR on methionine and folate metabolism are discussed... - Structural and spectroscopic characterization of P450 BM3 mutants with unprecedented P450 heme iron ligand sets. New heme ligation states influence conformational equilibria in P450 BM3Hazel M Girvan
School of Chemical Engineering and Analytical Science, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, UK
J Biol Chem 282:564-72. 2007.... - Crystal structure and solution characterization of the activation domain of human methionine synthaseKirsten R Wolthers
Faculty of Life Sciences, University of Manchester, UK
FEBS J 274:738-50. 2007..The reported structure is a component of the multidomain hMS : MSR complex, and represents an important step in understanding the impact of clinical mutations and polymorphisms in this key electron transfer complex... - New insights into the reductive half-reaction mechanism of aromatic amine dehydrogenase revealed by reaction with carbinolamine substratesAnna Roujeinikova
Manchester Interdisciplinary Biocenter, University of Manchester, Manchester M17DN, United Kingdom
J Biol Chem 282:23766-77. 2007..Slow hydrolysis of the amide occurs after, rather than prior to, TTQ oxidation and leads ultimately to a carboxylic acid product... - Structural and functional studies on DHC, the diheme cytochrome c from Rhodobacter sphaeroides, and its interaction with SHP, the sphaeroides heme proteinHelen R Gibson
School of Chemistry, University of Edinburgh, UK
Biochemistry 45:6363-71. 2006..These potentials are unaltered upon complex formation... - Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosisChristopher G Mowat
Institute of Cell and Molecular Biology, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, Scotland
Acta Crystallogr D Biol Crystallogr 58:704-5. 2002..3, c = 265.6 A. Native data have been collected to 1.6 A resolution and Hg-derivative data to 2.5 A resolution using a synchrotron-radiation source... - Role of His505 in the soluble fumarate reductase from Shewanella frigidimarinaKatherine L Pankhurst
Department of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, United Kingdom
Biochemistry 41:8551-6. 2002..The combined crystallographic and kinetic results suggest that His505 is not essential for sodium binding but does affect catalytic activity perhaps by influencing the pK(a) of the adjacent His504... - Engineering water to act as an active site acid catalyst in a soluble fumarate reductaseChristopher G Mowat
Department of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, Scotland, U K
Biochemistry 41:11990-6. 2002..However, in this mutant enzyme Michaelis complex formation is impaired due to significant and unpredicted structural changes at the active site... - The TB structural genomics consortium: providing a structural foundation for drug discoveryCelia W Goulding
Bioscience Division, Mail Stop M888, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
Curr Drug Targets Infect Disord 2:121-41. 2002..The Consortium has determined structures of 28 proteins from TB to date. These protein structures are already providing a basis for drug discovery efforts... - Mutagenesis of morphinone reductase induces multiple reactive configurations and identifies potential ambiguity in kinetic analysis of enzyme tunneling mechanismsChristopher R Pudney
Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester, M1 7DN, U K
J Am Chem Soc 129:13949-56. 2007..Implications for the interpretation from kinetic data of tunneling mechanisms in enzymes are discussed... - Molecular basis of halorespiration control by CprK, a CRP-FNR type transcriptional regulatorColin Levy
Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester M1 7DN, UK
Mol Microbiol 70:151-67. 2008..This suggests that, despite significant structural homology, distinct allosteric mechanisms are used, enabling this protein family to control a very wide range of processes... - The preponderance of P450s in the Mycobacterium tuberculosis genomeKirsty J McLean
Manchester Interdisciplinary Biocentre, School of Chemical Engineering and Analytical Science and School of Life Sciences, University of Manchester, Jackson's Mill, Sackville Street, Manchester, UK, M60 1QD
Trends Microbiol 14:220-8. 2006..Elucidation of structure, function and metabolic roles will be essential in targeting the P450s as an 'Achilles heel' in this major human pathogen... - Atomic description of an enzyme reaction dominated by proton tunnelingLaura Masgrau
Manchester Interdisciplinary Biocentre, University of Manchester, Jackson's Mill, Post Office Box 88, Manchester M60 1QD, UK
Science 312:237-41. 2006..We show that, in this enzyme system, tunneling is promoted by a short-range motion modulating proton-acceptor distance and no long-range coupled motion is required... - Catalysis by the isolated tryptophan tryptophylquinone-containing subunit of aromatic amine dehydrogenase is distinct from native enzyme and synthetic model compounds and allows further probing of TTQ mechanismParvinder Hothi
Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, UK
Biochemistry 47:183-94. 2008..This is attributed to the absence of structural rearrangement prior to H-transfer that limits the rate of TTQ reduction by para-substituted benzylamines in native enzyme... - Atomistic insight into the origin of the temperature-dependence of kinetic isotope effects and H-tunnelling in enzyme systems is revealed through combined experimental studies and biomolecular simulationSam Hay
Manchester Interdisciplinary Biocentre and Faculty of Life Science, University of Manchester, 131 Princess Street, Manchester M1 7DN, U K
Biochem Soc Trans 36:16-21. 2008.... - Structure and mechanism of an unusual malonate decarboxylase and related racemasesKrzysztof Okrasa
School of Chemistry and Manchester Interdisciplinary Biocentre, The University of Manchester, 131 Princess Street, Manchester, UK
Chemistry 14:6609-13. 2008 - Isotope effects reveal that para-substituted benzylamines are poor reactivity probes of the quinoprotein mechanism for aromatic amine dehydrogenaseParvinder Hothi
Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, UK
Biochemistry 46:9250-9. 2007.... - Mechanistic aspects and redox properties of hyperthermophilic L-proline dehydrogenase from Pyrococcus furiosus related to dimethylglycine dehydrogenase/oxidasePhillip J Monaghan
Manchester Interdisciplinary Biocentre and Faculty of Life Sciences, University of Manchester, UK
FEBS J 274:2070-87. 2007..These studies provide the first detailed account of the kinetic/redox properties of this hyperthermophilic L-proline dehydrogenase. Implications for its mechanism of action are discussed... - Transcriptional activation by CprK1 is regulated by protein structural changes induced by effector binding and redox stateHortense Mazon
Department of Biomolecular Mass Spectrometry, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands
J Biol Chem 282:11281-90. 2007.... - Atomic level insight into the oxidative half-reaction of aromatic amine dehydrogenaseAnna Roujeinikova
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
J Biol Chem 281:40264-72. 2006.... - Hydrogen tunnelling in enzyme-catalysed H-transfer reactions: flavoprotein and quinoprotein systemsMichael J Sutcliffe
Manchester Interdisciplinary Biocentre, School of Chemical Engineering and Analytical Science, Faculty of Life Sciences, University of Manchester, UK
Philos Trans R Soc Lond B Biol Sci 361:1375-86. 2006..Furthermore, tunnelling mechanisms in enzymes are supported by atomistic computational studies performed within the framework of modern TST, which incorporates quantum nuclear effects... - CprK crystal structures reveal mechanism for transcriptional control of halorespirationM Gordon Joyce
Manchester Interdisciplinary Biocentre, P. O. Box 88, Manchester, M60 1QD, United Kingdom
J Biol Chem 281:28318-25. 2006..These structures provide a structural framework for further studies on transcriptional control by CRP-FNR homologs in general and of halorespiration regulation by CprK in particular... - Lys-D48 is required for charge stabilization, rapid flavin reduction, and internal electron transfer in the catalytic cycle of dihydroorotate dehydrogenase B of Lactococcus lactisJonathan P Combe
Faculty of Life Sciences, Manchester Interdisciplinary Biocentre, University of Manchester, Jackson's Mill, Sackville Street, Manchester M60 1QD, United Kingdom
J Biol Chem 281:17977-88. 2006.... - Tryptophan tryptophylquinone cofactor biogenesis in the aromatic amine dehydrogenase of Alcaligenes faecalis. Cofactor assembly and catalytic properties of recombinant enzyme expressed in Paracoccus denitrificansParvinder Hothi
Manchester Interdisciplinary Biocentre and Faculty of Life Sciences, University of Manchester, UK
FEBS J 272:5894-909. 2005..1 and 9.3, again with the maximum value realized in the alkaline region. The potential origin of these kinetically influential ionizations is discussed... - The dimeric form of flavocytochrome P450 BM3 is catalytically functional as a fatty acid hydroxylaseRajasekhar Neeli
Manchester Interdisciplinary Biocentre, School of Chemical Engineering and Analytical Science, The University of Manchester, Jackson's Mill, UK
FEBS Lett 579:5582-8. 2005..Fatty acid oxidation is reconstituted by mixing inactive oxygenase (A264H) and FMN-depleted (G570D) mutants, demonstrating that inter-monomer (FMN(1)-to-heme(2)) electron transfer supports oxygenase activity in the BM3 dimer...