The X-Ray Crystal Structure of the Human Mono-Oxygenase Cytochrome P450 3A5-Ritonavir Complex Reveals Active Site Differences between P450s 3A4 and 3A5.

ABSTRACT: The contributions of cytochrome P450 3A5 to the metabolic clearance of marketed drugs is unclear, but its probable role is to augment the metabolism of several drugs that are largely cleared by P450 3A4. Selective metabolism by 3A4 is often a concern in drug development owing to potential drug-drug interactions and the variability of 3A4 and 3A5 expression. The contribution of P450 3A5 to these clearance pathways varies between individuals owing to genetic differences and similarities and differences in the metabolic properties of 3A5 compared with 3A4. To better understand the structural differences between P450s 3A4 and 3A5, the structure of 3A5 complexed with ritonavir was determined by X-ray crystallography to a limiting resolution of 2.91 Å. The secondary and tertiary structures of 3A

SUBMITTER: Hsu MH 

PROVIDER: S-EPMC5708090 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature