Crucial gating residues govern the enhancement of peroxygenase activity in an engineered cytochrome P450 O-demethylase.

ABSTRACT: P450-catalyzed O-demethylation reactions have recently attracted particular attention because of their potential applications in lignin bioconversion. We recently enabled the peroxygenase activity of CYP199A4, a NADH-dependent cytochrome P450 monooxygenase from Rhodopseudomonas palustris, by engineering a hydrogen peroxide (H₂O₂) tunnel. In this report, we reveal by crystallography and molecule dynamics simulations that key residues located at one of the water tunnels in CYP199A4 play a crucial gating role, which enhances the peroxygenase activity by regulating the inflow of H₂O₂. These results provide a more complete understanding of the mechanism by which monooxygenase is converted into peroxygenase activity through the H₂

SUBMITTER: Zhao P 

PROVIDER: S-EPMC11134341 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature