title: Molecular modelling of steroidogenic cytochromes P450 from families CYP11, CYP17, CYP19 and CYP21 based on the CYP102 crystal structure.
abstract: The results of homology modelling of mammalian steroidogenic cytochromes P450 (CYP) from families CYP11, CYP17, CYP19 and CYP21 are reported, based on a novel protein sequence alignment with CYP102, a bacterial P450 of known crystal structure. 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. Interactive docking studies with both substrates and inhibitors of these enzymes indicate key residue interactions with the putative active site regions of each isoform investigated, which point to potential determinants of substrate specificity within these related enzymes.
authors.affiliation: Molecular Toxicology Group, Centre for Toxicology, School of Biological Sciences, University of Surrey, Guildford, UK. d.lewis@surrey.ac.uk
authors.forename: D F
authors.initials: DF
authors.lastname: Lewis
authors.forename: P
authors.initials: P
authors.lastname: Lee-Robichaud
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001141:Aromatase / Q000737:chemistry; D001426:Bacterial Proteins; D001665:Binding Sites; D002417:Cattle; D003196:Computer Graphics; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D006728:Hormones / Q000096:biosynthesis / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D006899:Mixed Function Oxygenases; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009251:NADPH-Ferrihemoprotein Reductase; D017354:Point Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013252:Steroid 11-beta-Hydroxylase / Q000737:chemistry; D013254:Steroid 17-alpha-Hydroxylase / Q000737:chemistry; D013255:Steroid 21-Hydroxylase / Q000737:chemistry; D013256:Steroids / Q000096:biosynthesis / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D006728:Hormones; D011994:Recombinant Proteins; D013256:Steroids; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001141:Aromatase; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases