Conformational Response of N-Terminally Truncated Cytochrome P450 3A4 to Ligand Binding in Solution.

ABSTRACT: Human cytochrome P450 3A4 (CYP3A4) is a membrane-associated monooxygenase that is responsible for metabolizing >50% of the pharmaceuticals in the current market, so studying its chemical mechanism and structural changes upon ligand binding will help provide deeper insights into drug metabolism and further drug development. The best-characterized cytochrome P450 is a bacterial form, P450cam, which undergoes significant conformational changes upon binding substrate and its redox partner, putidaredoxin. In contrast, most crystal structures of CYP3A4 with or without ligands have shown few changes, although allosteric effects and multiple-substrate binding in solution are well-documented. In this study, we use double electron-electron resonance (DEER) to measure distances between spatially sepa

SUBMITTER: Chuo SW 

PROVIDER: S-EPMC7048403 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature