title: Modelling species selectivity in rat and human cytochrome P450 2D enzymes.
abstract: Updated models of the Rat Cytochrome P450 2D enzymes are produced based on the recent x-ray structures of the Human P450 2D6 enzyme both with and without a ligand bound. The differences in species selectivity between the epimers quinine and quinidine are rationalised using these models and the results are discussed with regard to previous studies. A close approach to the heme is not observed in this study. The x-ray structure of the enzyme with a ligand bound is shown to be a better model for explaining the observed experimental binding of quinine and quinidine. Hence models with larger closed binding sites are recommended for comparative docking studies. This is consistent with molecular recognition in Cytochrome P450 enzymes being the result of a number of non-specific interactions in a large binding site.
authors.affiliation: Department of Chemistry, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
authors.forename: Grace H C
authors.initials: GH
authors.lastname: Edmund
authors.forename: David F V
authors.initials: DF
authors.lastname: Lewis
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Howlin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D019389:Cytochrome P-450 CYP2D6 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011802:Quinidine / Q000737:chemistry / Q000378:metabolism; D011803:Quinine / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013237:Stereoisomerism
chemical_list: D008024:Ligands; D011803:Quinine; D019389:Cytochrome P-450 CYP2D6; D011802:Quinidine