QM/MM Study of the Reaction Mechanism of L-Tyrosine Hydroxylation Catalyzed by the Enzyme CYP76AD1.

ABSTRACT: We have studied the hydroxylation mechanism of l-Tyr by the heme-dependent enzyme CYP76AD1 from the sugar beet (Beta vulgaris). This enzyme has a promising biotechnological application in modified yeast strains to produce medicinal alkaloids, an alternative to the traditional opium poppy harvest. A generative machine learning software based on AlphaFold was used to build the structure of CYP76AD1 since there are no structural data for this specific enzyme. After model validation, l-Tyr was docked in the active site of CYP76AD1 to assemble the reactive complex, whose catalytic distances remained stable throughout the 100 ns of MD simulation. Subsequent QM/MM calculations elucidated that l-Tyr hydroxylation occurs in two steps: hydrogen abstraction from l-Tyr by CpdI, forming an l-Tyr

SUBMITTER: Sousa JPM 

PROVIDER: S-EPMC11457145 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature