D F V Lewis

Summary

Affiliation: University of Surrey
Country: UK

Publications

  1. ncbi Quantitative structure-activity relationships (QSARs) for substrates of human cytochromes P450 CYP2 family enzymes
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, GU2 7XH, UK
    Toxicol In Vitro 18:89-97. 2004
  2. ncbi 57 varieties: the human cytochromes P450
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, UK
    Pharmacogenomics 5:305-18. 2004
  3. ncbi Quantitative structure-activity relationships (QSARs) within cytochromes P450 2B (CYP2B) subfamily enzymes: the importance of lipophilicity for binding and metabolism
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 21:213-31. 2006
  4. ncbi Molecular modelling of CYP2F substrates: comparison of naphthalene metabolism by human, rat and mouse CYP2F subfamily enzymes
    David F V Lewis
    Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 24:229-57. 2009
  5. ncbi Homology modelling of CYP3A4 from the CYP2C5 crystallographic template: analysis of typical CYP3A4 substrate interactions
    D F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford 2GU2 7XH, UK
    Xenobiotica 34:549-69. 2004
  6. ncbi Quantitative structure-activity relationships within a homologous series of 7-alkoxyresorufins exhibiting activity towards CYP1A and CYP2B enzymes: molecular modelling studies on key members of the resorufin series with CYP2C5-derived models of human CYP1
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK
    Xenobiotica 34:501-13. 2004
  7. ncbi Compound lipophilicity for substrate binding to human P450s in drug metabolism
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Discov Today 9:530-7. 2004
  8. ncbi Investigation of enzyme selectivity in the human CYP2C subfamily: homology modelling of CYP2C8, CYP2C9 and CYP2C19 from the CYP2C5 crystallographic template
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 19:257-85. 2003
  9. ncbi A molecular model of CYP2D6 constructed by homology with the CYP2C5 crystallographic template: investigation of enzyme-substrate interactions
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 19:189-210. 2003
  10. ncbi On the estimation of binding affinity (deltaGbind) for human P450 substrates (based on Km and KD values)
    David F V Lewis
    Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    Curr Drug Metab 4:331-40. 2003

Detail Information

Publications74

  1. ncbi Quantitative structure-activity relationships (QSARs) for substrates of human cytochromes P450 CYP2 family enzymes
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, GU2 7XH, UK
    Toxicol In Vitro 18:89-97. 2004
    ....
  2. ncbi 57 varieties: the human cytochromes P450
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, UK
    Pharmacogenomics 5:305-18. 2004
    ..This review covers the extent of enzyme functionality for the known human P450s, focusing primarily on their role in the Phase I metabolism of foreign compounds, which involves the CYP1, CYP2 and CYP3 families...
  3. ncbi Quantitative structure-activity relationships (QSARs) within cytochromes P450 2B (CYP2B) subfamily enzymes: the importance of lipophilicity for binding and metabolism
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 21:213-31. 2006
    ..In addition, there is a remarkable similarity in the coefficients for the log P term of any QSAR expression, which suggests that the hydrophobicity of CYP2B active sites may be broadly equivalent between the various mammalian species...
  4. ncbi Molecular modelling of CYP2F substrates: comparison of naphthalene metabolism by human, rat and mouse CYP2F subfamily enzymes
    David F V Lewis
    Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 24:229-57. 2009
    ..It is noted that the CYP2F subfamily enzymes are associated with the activation of naphthalene in all three mammalian species, although there are marked differences between man and the two rodent species in the toxicity of this compound...
  5. ncbi Homology modelling of CYP3A4 from the CYP2C5 crystallographic template: analysis of typical CYP3A4 substrate interactions
    D F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford 2GU2 7XH, UK
    Xenobiotica 34:549-69. 2004
    ..4. Typical CYP3A4 substrates, such as midazolam, testosterone, nifedipine and verapamil, are shown to fit the putative active site of the enzyme structure in a manner consistent with their known positions of metabolism...
  6. ncbi Quantitative structure-activity relationships within a homologous series of 7-alkoxyresorufins exhibiting activity towards CYP1A and CYP2B enzymes: molecular modelling studies on key members of the resorufin series with CYP2C5-derived models of human CYP1
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK
    Xenobiotica 34:501-13. 2004
    ....
  7. ncbi Compound lipophilicity for substrate binding to human P450s in drug metabolism
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Discov Today 9:530-7. 2004
    ....
  8. ncbi Investigation of enzyme selectivity in the human CYP2C subfamily: homology modelling of CYP2C8, CYP2C9 and CYP2C19 from the CYP2C5 crystallographic template
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 19:257-85. 2003
    ..97 and 0.99 depending on the QSAR equation produced...
  9. ncbi A molecular model of CYP2D6 constructed by homology with the CYP2C5 crystallographic template: investigation of enzyme-substrate interactions
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 19:189-210. 2003
    ..Calculation of substrate binding affinity based on contributions from active site interactions and lipophilic character gives satisfactory agreement with experimentally determined KD values...
  10. ncbi On the estimation of binding affinity (deltaGbind) for human P450 substrates (based on Km and KD values)
    David F V Lewis
    Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    Curr Drug Metab 4:331-40. 2003
    ..However, the appearance of a small constant term in the QSAR equation could possibly relate to an average loss in translational and rotational energy for the 90 compounds studied in this investigation...
  11. ncbi Structural models for cytochrome P450-mediated catalysis
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, UK
    ScientificWorldJournal 3:536-45. 2003
    ....
  12. ncbi P450 structures and oxidative metabolism of xenobiotics
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    Pharmacogenomics 4:387-95. 2003
    ..As an important example of biocatalysis, the P450 system has a major future as an enzyme for use in many biotechnological applications, including biodegradation and bioremediation...
  13. ncbi Molecular binding interactions: their estimation and rationalization in QSARs in terms of theoretically derived parameters
    David F V Lewis
    Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    ScientificWorldJournal 2:1776-802. 2002
    ..The lipophilic parameter, log P, and its relevance to desolvation energy is outlined and explanation of the parameters derived from electronic structure calculation is provided, leading into a summary of molecular dynamics simulations...
  14. ncbi Cytochromes P450, oxygen, and evolution
    D F Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    ScientificWorldJournal 1:151-67. 2001
    ....
  15. ncbi Molecular modelling of CYP2B6 based on homology with the CYP2C5 crystal structure: analysis of enzyme-substrate interactions
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 19:115-35. 2002
    ..It is possible to estimate the binding energies for typical CYP2B6 substrates based on their properties and interactions with the enzyme, which show good concordance with experimental data in the form of apparent Km values...
  16. ncbi Molecular modelling of the mouse cytochrome P450 CYP2F2 based on the CYP102 crystal structure template and selective CYP2F2 substrate interactions
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 19:97-113. 2002
    ..This procedure can therefore be used to investigate the potential for activation of xenobiotics via this enzyme, especially those related to known CYP2F substrates, such as naphthalene...
  17. ncbi Molecular modelling of human CYP1B1 substrate interactions and investigation of allelic variant effects on metabolism
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK
    Chem Biol Interact 145:281-95. 2003
    ....
  18. ncbi Substrates of human cytochromes P450 from families CYP1 and CYP2: analysis of enzyme selectivity and metabolism
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metabol Drug Interact 20:111-42. 2004
    ....
  19. ncbi Hydrogen bonding in human p450-substrate interactions: a major contribution to binding affinity
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    ScientificWorldJournal 4:1074-82. 2004
    ....
  20. ncbi Molecular modelling of human microsomal epoxide hydrolase (EH) by homology with a fungal (Aspergillus niger) EH crystal structure of 1.8 A resolution: structure-activity relationships in epoxides inhibiting EH activity
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    Toxicol In Vitro 19:517-22. 2005
    ....
  21. ncbi Human CYPs involved in drug metabolism: structures, substrates and binding affinities
    David F V Lewis
    University of Surrey, Faculty of Health and Medical Sciences, Surrey, UK
    Expert Opin Drug Metab Toxicol 6:661-74. 2010
    ..There is current interest in the CYPs primarily due to their important role in the Phase I metabolism of foreign compounds, including pharmaceuticals, agrochemicals and environmental pollutants, to which mankind is exposed...
  22. ncbi An evaluation of ondansetron binding interactions with human cytochrome P450 enzymes CYP3A4 and CYP2D6
    David F V Lewis
    Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    Drug Metab Lett 4:25-30. 2010
    ..Moreover, the modelled binding orientations for ondansetron in CYP2D6 and CYP3A4 are largely consistent with the NMR data and with the known routes for P450-mediated metabolism of this compound...
  23. ncbi Quantitative structure-activity relationships (QSARs) for inhibitors and substrates of CYP2B enzymes: importance of compound lipophilicity in explanation of potency differences
    David F V Lewis
    Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    J Enzyme Inhib Med Chem 25:679-84. 2010
    ..The findings from QSAR studies can be rationalized by molecular modelling of the active site interactions with both P450 crystal structures and homology models of CYP2B subfamily enzymes...
  24. ncbi Electronic and structural aspects of p450-mediated drug metabolism
    David F V Lewis
    Faculty of Health and Medical Sciences, Biomedical Sciences Division, University of Surrey, Guildford, Surrey GU27XH, UK
    Drug Metab Lett 3:87-100. 2009
    ..The importance of ionization potential as a factor in the overall catalytic turnover of P450-mediated reactions is noted, especially in combination with the lipophilicity parameter, log P...
  25. ncbi Human P450s involved in drug metabolism and the use of structural modelling for understanding substrate selectivity and binding affinity
    D F V Lewis
    Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
    Xenobiotica 39:625-35. 2009
    ..The combination of molecular modelling and quantitative structure-activity relationship (QSAR) studies facilitates understanding of the factors which determine substrate selectivity and binding to the human drug-metabolizing P450s...
  26. ncbi Human cytochromes P450 in the metabolism of drugs: new molecular models of enzyme-substrate interactions
    David Fv Lewis
    University of Surrey, Centre for Toxicology, Faculty of Health and Medical Sciences, Guildford, Surrey, UK
    Expert Opin Drug Metab Toxicol 4:1181-6. 2008
    ....
  27. ncbi Quantitative structure-activity relationships (QSARs) in inhibitors of various cytochromes P450: the importance of compound lipophilicity
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK
    J Enzyme Inhib Med Chem 22:1-6. 2007
    ....
  28. ncbi Lipophilicity relationships in inhibitors of CYP2C9 and CYP2C19 enzymes
    David F V Lewis
    School of Biomedical and Molecular Sciences University of Surrey, Guildford, Surrey, GU2 XH, UK
    J Enzyme Inhib Med Chem 21:385-9. 2006
    ..In addition, there is a role for hydrogen bonding and pi-pi stacking interactions within the P450 active site which represent secondary factors in the binding processes of these compounds...
  29. ncbi Structural modelling of the human drug-metabolizing cytochromes P450
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    Curr Med Chem 13:2645-52. 2006
    ....
  30. ncbi Human P450s in the metabolism of drugs: molecular modelling of enzyme-substrate interactions
    David F V Lewis
    University of Surrey, School of Biomedical and Molecular Sciences, Guildford, Surrey, GU2 7XH, UK
    Expert Opin Drug Metab Toxicol 1:5-8. 2005
    ..The relatively new technologies of molecular biology, protein crystallography and molecular modelling have been applied to these enzymes and this endeavour is proving extremely useful for novel compound development...
  31. ncbi Investigating human P450s involved in drug metabolism via homology with high-resolution P450 crystal structures of the CYP2C subfamily
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    Curr Drug Metab 7:589-98. 2006
    ..In particular, the homology models of human CYP1 and CYP2 family enzymes are presented, where good agreement with experiment findings are apparent...
  32. ncbi The astronomical pulse of global extinction events
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    ScientificWorldJournal 6:718-26. 2006
    ..The potential relevance of Milankovitch cycles is also explored in the light of current evidence for the possible causes of extinction events over a geological timescale...
  33. ncbi Quantitative structure-activity relationships (QSars) in CYP3A4 inhibitors: the importance of lipophilic character and hydrogen bonding
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK
    J Enzyme Inhib Med Chem 21:127-32. 2006
    ..In this respect, there appears to be good agreement between QSAR analyses and molecular modelling of the CYP3A4 enzyme itself, and both are consistent with the known mechanisms of inhibition displayed...
  34. ncbi Metabolism of coumarin by human P450s: a molecular modelling study
    David F V Lewis
    School of Biomedical and Molecular Sciences, University of Surrey, Stag Hill, Guildford, Surrey GU2 7XH, UK
    Toxicol In Vitro 20:256-64. 2006
    ....
  35. ncbi Human cytochromes P450 associated with the phase 1 metabolism of drugs and other xenobiotics: a compilation of substrates and inhibitors of the CYP1, CYP2 and CYP3 families
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    Curr Med Chem 10:1955-72. 2003
    ..The compilation therefore assists in establishing substrate structure-activity relationships (SSARs) within human drug-metabolizing P450s...
  36. ncbi Baseline lipophilicity relationships in human cytochromes P450 associated with drug metabolism
    David F V Lewis
    Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, UK
    Drug Metab Rev 35:1-18. 2003
    ..This shows that there are common interactions for certain numbers of substrates in each case composed of hydrogen bonding and pi-pi stacking, the extent of which varies from one P450 enzyme to another...
  37. ncbi Factors influencing rates and clearance in P450-mediated reactions: QSARs for substrates of the xenobiotic-metabolizing hepatic microsomal P450s
    D F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK
    Toxicology 170:45-53. 2002
    ....
  38. ncbi Molecular modeling of human cytochrome P450-substrate interactions
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, UK
    Drug Metab Rev 34:55-67. 2002
    ..The self-consistency of these homology models indicates that they may have potential utility for the pre-screening of novel drug structures...
  39. ncbi Quantitative structure-activity relationships (QSARs) within series of inhibitors for mammalian cytochromes P450 (CYPs)
    D F Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, UK
    J Enzyme Inhib 16:321-30. 2001
    ..In general, there is close agreement (R = 0.95-0.99) between experimental pKi values and those calculated via QSAR analysis...
  40. ncbi Quantitative structure-activity relationships (QSARs) within substrates of human cytochromes P450 involved in drug metabolism
    D F Lewis
    Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, UK
    Drug Metabol Drug Interact 18:221-42. 2001
    ....
  41. ncbi Structural determinants of cytochrome P450 substrate specificity, binding affinity and catalytic rate
    D F Lewis
    School of Biological Sciences, University of Surrey, Guildford, UK
    Chem Biol Interact 115:175-99. 1998
    ..It is thus shown that the prediction of P450 substrate binding affinities and catalytic rates may be feasible, provided that sufficient structural information is available for the relevant enzyme-substrate complex...
  42. ncbi Molecular modelling of CYP2B6, the human CYP2B isoform, by homology with the substrate-bound CYP102 crystal structure: evaluation of CYP2B6 substrate characteristics, the cytochrome b5 binding site and comparisons with CYP2B1 and CYP2B4
    D F Lewis
    Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, UK
    Xenobiotica 29:361-93. 1999
    ....
  43. ncbi Modelling human cytochromes P450 for evaluating drug metabolism: an update
    D F Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK
    Drug Metabol Drug Interact 16:307-24. 2000
    ..It also represents an update on previously published work in this journal /1/...
  44. ncbi Molecular modelling of lanosterol 14 alpha-demethylase (CYP51) from Saccharomyces cerevisiae via homology with CYP102, a unique bacterial cytochrome P450 isoform: quantitative structure-activity relationships (QSARs) within two related series of antifunga
    D F Lewis
    School of Biological Sciences, University of Surrey, Guildford, UK
    J Enzyme Inhib 14:175-92. 1999
    ....
  45. ncbi On the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics: towards the prediction of human p450 substrate specificity and metabolism
    D F Lewis
    School of Biological Sciences, University of Surrey, Guildford, GU2 5XH, Surrey, UK
    Biochem Pharmacol 60:293-306. 2000
    ..Factors contributing to metabolic clearance and binding affinity are also discussed, and methods for their calculation are described...
  46. ncbi Structural characteristics of human P450s involved in drug metabolism: QSARs and lipophilicity profiles
    D F Lewis
    Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, UK
    Toxicology 144:197-203. 2000
    ..In addition, the physicochemical characteristics (logP and pK(a) values) of heptic microsomal P450 substrates are collated, such that comparisons can be made on the grounds of compound lipophilicities...
  47. ncbi Molecular modelling of human CYP2E1 by homology with the CYP102 haemoprotein domain: investigation of the interactions of substrates and inhibitors within the putative active site of the human CYP2E1 isoform
    D F Lewis
    Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, UK
    Xenobiotica 30:1-25. 2000
    ....
  48. ncbi Molecular modelling of CYP1 family enzymes CYP1A1, CYP1A2, CYP1A6 and CYP1B1 based on sequence homology with CYP102
    D F Lewis
    Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, UK
    Toxicology 139:53-79. 1999
    ....
  49. ncbi Molecular modelling of CYP4A subfamily members based on sequence homology with CYP102
    D F Lewis
    Molecular Toxicology Group, School of Biological Sciences, University of Surrey, UK
    Xenobiotica 29:763-81. 1999
    ..3. The differences in substrate specificity between CYP4A1, CYP4A11 and CYP4A4 towards fatty acids and prostaglandins respectively are rationalized in terms of variations in active site amino residues...
  50. ncbi Structure-activity relationship for human cytochrome P450 substrates and inhibitors
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, UK
    Drug Metab Rev 34:69-82. 2002
    ....
  51. ncbi Molecular modelling of the peroxisome proliferator-activated receptor alpha (PPAR alpha) from human, rat and mouse, based on homology with the human PPAR gamma crystal structure
    D F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK
    Toxicol In Vitro 16:275-80. 2002
    ....
  52. ncbi Homology modelling of human CYP2 family enzymes based on the CYP2C5 crystal structure
    D F V Lewis
    Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford GU2 7XH, UK
    Xenobiotica 32:305-23. 2002
    ..3. The results are consistent with reported findings from site-directed mutagenesis experiments with the CYP2 family, and with published information on substrate metabolism...
  53. ncbi A quantitative structure-activity relationship (QSAR) study of mutagenicity in several series of organic chemicals likely to be activated by cytochrome P450 enzymes
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Surrey, United Kingdom
    Teratog Carcinog Mutagen . 2003
    ....
  54. ncbi Substrate SARs in human P450s
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, UK GU2 7XH
    Drug Discov Today 7:918-25. 2002
    ..Importantly, the variation in binding affinities of 60 human CYP substrates can be explained by understanding the key physicochemical, structural and electronic characteristics that govern substrate binding to each isozyme...
  55. ncbi Homology modelling of human CYP2E1 based on the CYP2C5 crystal structure: investigation of enzyme-substrate and enzyme-inhibitor interactions
    D F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK
    Toxicol In Vitro 17:93-105. 2003
    ..This method has been based on a consideration of the active site interactions between substrates and key amino acid residues lining the haem pocket, together with compound lipophilicity data from partition coefficients...
  56. ncbi Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes
    David F V Lewis
    Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, UK
    Arch Biochem Biophys 409:32-44. 2003
    ..Molecular modeling studies based on the recent CYP2C5 crystal structure appear to show close agreement with site-directed mutagenesis experiments and with information on substrate metabolism and selectivity within the CYP2 family...
  57. ncbi Modelling human cytochromes P450 involved in drug metabolism from the CYP2C5 crystallographic template
    David F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, UK
    J Inorg Biochem 91:502-14. 2002
    ..Consequently, the CYP2C5 crystal structure can be regarded at the current paradigm for homology modelling of the drug metabolizing P450s, especially those from the CYP2 family...
  58. ncbi Molecular orbital calculations and nicotine metabolism: a rationale for experimentally observed metabolite ratios
    D F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, UK
    Drug Metabol Drug Interact 19:29-39. 2002
    ....
  59. ncbi Species differences in coumarin metabolism: a molecular modelling evaluation of CYP2A interactions
    D F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford GU2 7XH, UK
    Xenobiotica 32:547-61. 2002
    ....
  60. ncbi Molecular modelling of steroidogenic cytochromes P450 from families CYP11, CYP17, CYP19 and CYP21 based on the CYP102 crystal structure
    D F Lewis
    Molecular Toxicology Group, Centre for Toxicology, School of Biological Sciences, University of Surrey, Guildford, UK
    J Steroid Biochem Mol Biol 66:217-33. 1998
    ....
  61. ncbi Quantitative structure--activity relationships for inducers of cytochromes P450 and nuclear receptor ligands involved in P450 regulation within the CYP1, CYP2, CYP3 and CYP4 families
    D F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK
    Toxicology 176:51-7. 2002
    ....
  62. ncbi Homology modelling of human cytochromes P450 involved in xenobiotic metabolism and rationalization of substrate selectivity
    D F Lewis
    School of Biological Sciences, University of Surrey, UK
    Exp Toxicol Pathol 51:369-74. 1999
    ..A combination of homology model interactions with substrates and certain molecular properties of the compounds themselves provides a methodology for the evaluation of potential P450 selectivity in new chemical entities (NCEs)...
  63. ncbi Molecular modelling of the human glucocorticoid receptor (hGR) ligand-binding domain (LBD) by homology with the human estrogen receptor alpha (hERalpha) LBD: quantitative structure-activity relationships within a series of CYP3A4 inducers where induction
    D F V Lewis
    School of Biomedical and Life Sciences, University of Surrey, Surrey GU2 7XH, Guildford, UK
    J Steroid Biochem Mol Biol 82:195-9. 2002
    ..96-0.98) with fold induction of CYP3A4 known to be mediated via hGR involvement...
  64. ncbi Molecular modelling of CYP2E1 enzymes from rat, mouse and man: an explanation for species differences in butadiene metabolism and potential carcinogenicity, and rationalization of CYP2E substrate specificity
    D F Lewis
    Molecular Toxicology Group, Centre for Toxicology, School of Biological Sciences, University of Surrey, Guildford, UK
    Toxicology 118:93-113. 1997
    ....
  65. ncbi Molecular modelling of mammalian CYP2B isoforms and their interaction with substrates, inhibitors and redox partners
    D F Lewis
    School of Biological Sciences, University of Surrey, Guildford, UK
    Xenobiotica 27:443-78. 1997
    ..4. Molecular modelling of CYP2B isozymes appears to rationalize a number of the reported findings from quantitative structure-activity relationship investigations on series of CYP2B substrates and inhibitors...
  66. ncbi Metabolism of 2,5-bis(trifluoromethyl)-7-benzyloxy-4-trifluoromethylcoumarin by human hepatic CYP isoforms: evidence for selectivity towards CYP3A4
    A B Renwick
    TNO BIBRA International Ltd, Carshalton, Surrey, UK
    Xenobiotica 31:187-204. 2001
    ..BFBFC may be a useful fluorescent probe substrate for human hepatic CYP3A4, but compared with 7BQ has only a low rate of metabolism in human liver microsomes...
  67. ncbi Homology modelling of human CYP1A2 based on the CYP2C5 crystallographic template structure
    D F V Lewis
    Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford GU2 7XH, UK
    Xenobiotica 33:239-54. 2003
    ..4. The binding affinities of several CYP1A2 substrates have also been calculated from the CYP1A2 active site interactions and they agree closely with experimental values...
  68. ncbi Homology modelling of CYP2A6 based on the CYP2C5 crystallographic template: enzyme-substrate interactions and QSARs for binding affinity and inhibition
    D F V Lewis
    School of Biomedical, Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK
    Toxicol In Vitro 17:179-90. 2003
    ..The latter approach appears to represent a highly correlated (R=0.99) method for estimating the relative strength of enzyme-substrate binding within CYP2A6-selective compounds, albeit within a fairly limited dataset of substrates...
  69. ncbi Interactions between redox partners in various cytochrome P450 systems: functional and structural aspects
    D F Lewis
    Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, Surrey GU2 5XH, UK
    Biochim Biophys Acta 1460:353-74. 2000
    ....
  70. ncbi Homology modelling of the nuclear receptors: human oestrogen receptorbeta (hERbeta), the human pregnane-X-receptor (PXR), the Ah receptor (AhR) and the constitutive androstane receptor (CAR) ligand binding domains from the human oestrogen receptor alpha (
    M N Jacobs
    Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, UK
    J Steroid Biochem Mol Biol 84:117-32. 2003
    ....
  71. ncbi Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices
    D J Skene
    School of Biological Sciences, University of Surrey, Guildford, Surrey, GU2 5XH, UK
    J Pineal Res 31:333-42. 2001
    ..Collectively, all the above data provide strong experimental evidence that CYP1A2 is an important catalyst of the 6-hydroxylation of melatonin...
  72. ncbi COMPACT and molecular structure in toxicity assessment: a prospective evaluation of 30 chemicals currently being tested for rodent carcinogenicity by the NCI/NTP
    D F Lewis
    School of Biological Sciences, University of Surrey, Guildford, United Kingdom
    Environ Health Perspect 104:1011-6. 1996
    ....
  73. ncbi Studies on the acute effects of coumarin and some coumarin derivatives in the rat
    B G Lake
    BIBRA Toxicology International, Carshalton, Surrey, UK
    Food Chem Toxicol 32:357-63. 1994
    ..e. 3-MC, 4-MC and 3,4-DMC) leads to a reduction in coumarin-induced hepatotoxicity, due to diminished formation of 3,4-epoxide intermediates, was confirmed by the results of molecular orbital calculations...
  74. ncbi Human carcinogens: an evaluation study via the COMPACT and HazardExpert procedures
    D F V Lewi
    Molecular Toxicology Group, School of Biomedical and Life Sciences, University of Surrey, Guildford, UK
    Hum Exp Toxicol 21:115-22. 2002
    ..e., less than 1 hour per chemical) and at a low cost...