Molecular Determinants of Substrate Affinity and Enzyme Activity of a Cytochrome P450_BM3 Variant.

ABSTRACT: Cytochrome P450_BM3 catalyzes the hydroxylation and/or epoxidation of fatty acids, fatty amides, and alcohols. Protein engineering has produced P450_BM3 variants capable of accepting drug molecules normally metabolized by human P450 enzymes. The enhanced substrate promiscuity has been attributed to the greater flexibility of the lid of the substrate channel. However, it is not well understood how structurally different and highly polar drug molecules can stably bind in the active site nor how the activity and coupling efficiency of the enzyme may be affected by the lack of enzyme-substrate complementarity. To address these important aspects of non-native small molecule binding, this study investigated the binding of drug molecules with different size, charge, polar surf

SUBMITTER: Geronimo I 

PROVIDER: S-EPMC6170655 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature