Structural basis for regiospecific midazolam oxidation by human cytochrome P450 3A4.

ABSTRACT: Human cytochrome P450 3A4 (CYP3A4) is a major hepatic and intestinal enzyme that oxidizes more than 60% of administered therapeutics. Knowledge of how CYP3A4 adjusts and reshapes the active site to regioselectively oxidize chemically diverse compounds is critical for better understanding structure-function relations in this important enzyme, improving the outcomes for drug metabolism predictions, and developing pharmaceuticals that have a decreased ability to undergo metabolism and cause detrimental drug-drug interactions. However, there is very limited structural information on CYP3A4-substrate interactions available to date. Despite the vast variety of drugs undergoing metabolism, only the sedative midazolam (MDZ) serves as a marker substrate for the in vivo activity assessment because i

SUBMITTER: Sevrioukova IF 

PROVIDER: S-EPMC5255590 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature