Cooperative inhibition in cytochrome P450 between a substrate and an apparent noncompetitive inhibitor.

ABSTRACT: Cytochrome P450 (CYP) enzymes bind a heme group that acts as a catalytic center. Inhibition mechanisms in CYP enzymes have been studied extensively by biochemical and structural analyses. Noncompetitive inhibitors are generally believed to bind to allosteric sites remote from the active site to form enzyme-substrate-inhibitor (ESI) complexes. Docking simulations predict the binding sites of noncompetitive inhibitors to CYP enzymes, but to date, there has been no experimental structural verification of ESI complexes formed by CYP enzymes. We performed biochemical and structural analyses of CYP105A1 using the imidazole-containing inhibitors ketoconazole, lanoconazole, and miconazole. Enzyme inhibition analyses demonstrated that ketoconazole and miconazole act as competitive inhibitors, where

SUBMITTER: Hirano Y 

PROVIDER: S-EPMC12144444 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature