Structure and function of cytochromes P450 2B: from mechanism-based inactivators to X-ray crystal structures and back.

ABSTRACT: This article reviews work from the author dating back to 1978 and focuses on the structural basis of cytochrome P450 (P450) function using available contemporary techniques. Early studies used mechanism-based inactivators that bound to the protein moiety of hepatic P450s to try to localize the active site. Subsequent studies used cDNA cloning, heterologous expression, site-directed mutagenesis, and homology modeling based on multiple bacterial P450 X-ray crystal structures to predict the active sites of CYP2B enzymes with considerable accuracy. Breakthroughs in engineering and expression of mammalian P450s enabled us to determine our first X-ray crystal structure of ligand-free rabbit CYP2B4. To date, we have solved 11 CYP2B4 and three human CYP2B6 structures, which represent four signific

SUBMITTER: Halpert JR 

PROVIDER: S-EPMC3127236 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature