Hydroxylation Regiochemistry Is Robust to Active Site Mutations in Cytochrome P450_cam (CYP101A1).

ABSTRACT: Cytochrome P450_cam (CYP101A1) catalyzes the hydroxylation of d-camphor by molecular oxygen. The enzyme-catalyzed hydroxylation exhibits a high degree of regioselectivity and stereoselectivity, with a single major product, d-5-exo-hydroxycamphor, suggesting that the substrate is oriented to facilitate this specificity. In previous work, we used an elastic network model and perturbation response scanning to show that normal deformation modes of the enzyme structure are highly responsive not only to the presence of a substrate but also to the substrate orientation. This work examines the effects of mutations near the active site on substrate localization and orientation. The investigated mutations were designed to promote a change in substrate orientation and/or location tha

SUBMITTER: Alvarez G 

PROVIDER: S-EPMC9721313 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature