H₂O₂-Driven Hydroxylation of Steroids Catalyzed by Cytochrome P450 CYP105D18: Exploration of the Substrate Access Channel.

ABSTRACT: CYP105D18 supports H₂O₂ as an oxygen surrogate for catalysis well and shows high H₂O₂ resistance capacity. We report the hydroxylation of different steroids using H₂O₂ as a cosubstrate. Testosterone was regiospecifically hydroxylated to 2β-hydroxytestosterone. Based on the experimental data and molecular docking, we predicted that hydroxylation of methyl testosterone and nandrolone would occur at position 2 in the A-ring, while hydroxylation of androstenedione and adrenosterone was predicted to occur in the B-ring. Further, structure-guided rational design of the substrate access channel was performed with the mutagenesis of residues S63, R82, and F184. Among the mutants, S63A showed a marked decrease in product formation, w

SUBMITTER: Pardhe BD 

PROVIDER: S-EPMC9888293 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature