Microsomal cytochrome P450 2C5: comparison to microbial P450s and unique features.
Although microsomal P450s represent the majority of P450s, only microbial P450s have been amenable to crystal structure solution. We have recently solved the first crystal structure of a microsomal P450, 2C5, a progesterone hydroxylase from rabbit. We discuss the features of the protein in common with existing structures of microbial P450s and limitations of homology modeling mammalian P450s based on the microbial structures. Unique features involving membrane, substrate and cytochrome P450 reductase interactions are also discussed.
Williams
P A
PA
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cosme
J
J
Sridhar
V
V
Johnson
E F
EF
McRee
D E
DE
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D000072467:Cytochrome P450 Family 2; D008861:Microsomes / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000737:chemistry*; D008958:Models, Molecular; D009154:Mutation; D009251:NADPH-Ferrihemoprotein Reductase / Q000737:chemistry / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011817:Rabbits; D013255:Steroid 21-Hydroxylase / Q000737:chemistry*; D013379:Substrate Specificity
D011374:Progesterone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C065407:CYP2C5 protein, Oryctolagus cuniculus; D000072467:Cytochrome P450 Family 2; D013255:Steroid 21-Hydroxylase; D009251:NADPH-Ferrihemoprotein Reductase