The structure of microsomal cytochrome P450 2C5: a steroid and drug metabolizing enzyme.
The structure of microsomal P450 2C5 is the first structure of a membrane P450 to be determined by x-ray diffraction. This enzyme was originally identified as a progesterone 21-hydroxylase that is polymorphically expressed in rabbit liver. In contrast to the adrenal 21-hydroxylase, P450 2C5 metabolizes structurally diverse substrates that include a variety of steroids as well as therapeutic drugs. The flexible architecture of the enzyme and the residual solvation of the substrate provide a basis for understanding the catalytic diversity of 2C5 and related drug metabolizing P450s. In addition, the structure of P450 2C5 suggests how mammalian P450s have adapted for membrane binding and interaction with microsomal P450 reductase.
Johnson
Eric F
EF
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA. johnson@scripps.edu
Wester
Michael R
MR
Stout
C David
CD
D000818:Animals; D002384:Catalysis; D003460:Crystallization; D003461:Crystallography; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D006801:Humans; D008861:Microsomes / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013255:Steroid 21-Hydroxylase / Q000737:chemistry* / Q000378:metabolism; D013256:Steroids / Q000378:metabolism
D004364:Pharmaceutical Preparations; D013256:Steroids; D003577:Cytochrome P-450 Enzyme System; C065407:CYP2C5 protein, Oryctolagus cuniculus; D000072467:Cytochrome P450 Family 2; D013255:Steroid 21-Hydroxylase