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Cytochromes P450: structure, function and mechanism.
Part 1 Introduction: historical background isolation, purification and characterization spectral and related physiochemical properties substrate-binding spectra polarized optical spectroscopyExpand
Guide to Cytochromes P450 : structure and function
  • D. Lewis
  • Chemistry, Physics
  • 23 August 2001
1. Introduction 2. Evolution of the P450 superfamily 3. The P450 catalytic cycle 4. Substrate selectivity and metabolism 5. Regulation of P450 enzymes 6. The structures of cytochromes P450
Cytochromes P450 in the bioactivation of chemicals.
TLDR
The function of cytochromes P450 in the bioactivation of chemicals is currently being exploited to design systems that can be used clinically to facilitate the metabolic conversion of prodrugs to their biologically-active metabolites in cells that poorly express them in the so-called gene-directed prodrug therapy. Expand
On the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics: towards the prediction of human p450 substrate specificity and metabolism.
  • D. Lewis
  • Biology, Medicine
  • Biochemical pharmacology
  • 1 August 2000
TLDR
Molecular templates of superimposed substrates are shown to be complementary with the putative active sites of the relevant enzymes, thus enabling a possible prediction of P450 specificity from structure. Expand
The CYP2 family: models, mutants and interactions.
  • D. Lewis
  • Biology, Medicine
  • Xenobiotica; the fate of foreign compounds in…
  • 1998
TLDR
The homology models of CYP2 family enzymes appear to show self-consistency with the currently accumulated information from site-directed mutagenesis and chemical modification of amino acid residues known to affect redox partner interactions. Expand
Interactions between redox partners in various cytochrome P450 systems: functional and structural aspects.
TLDR
Molecular modeling of the interactions between the redox components in various P450 mono-oxygenase systems is proposed on the basis of structural and mutagenesis information, together with experimental findings based on chemical modification of key residues likely to be associated with complementary binding sites on certain typical P450 isoforms and their respective redox partners. Expand
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.
  • D. Lewis
  • Chemistry, Medicine
  • Current medicinal chemistry
  • 30 September 2003
TLDR
There are certain commonalities between substrates for the same enzyme, especially with respect to their positions of metabolism and likely interactions with the relevant enzyme active site regions, which assists in establishing substrate structure-activity relationships (SSARs) within human drug-metabolizing P450s. Expand
57 varieties: the human cytochromes P450.
  • D. Lewis
  • Biology, Medicine
  • Pharmacogenomics
  • 4 November 2004
TLDR
The extent of enzyme functionality for the known human P450s is covered, focusing primarily on their role in the Phase I metabolism of foreign compounds, which involves the CYP1, CYP2 and CYP3 families. Expand
Evolution of the cytochrome P450 superfamily: sequence alignments and pharmacogenetics.
TLDR
A number of key correspondences between the evolution of P450 system and the course of biological development over time, point to a mechanistic molecular biology of evolution which is consistent with a steady increase in atmospheric oxygenation beginning over 2000 million years ago, whereas dietary changes during more recent geological time may provide one possible explanation for certain species differences in metabolism. Expand
Molecular modelling of steroidogenic cytochromes P450 from families CYP11, CYP17, CYP19 and CYP21 based on the CYP102 crystal Structure
TLDR
The molecular models generated from the CYP102 crystal structure template are consistent with experimental information from site-directed mutagenesis studies, steroidal substrate specificity and active site inhibitor studies, and point to potential determinants of substrate specificity within these related enzymes. Expand
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