Mechanistic insights into the selective oxidation of D-arginine by the nonheme iron-dependent viomycin biosynthesis enzyme VioC.

ABSTRACT: VioC, a nonheme iron enzyme, catalyzes different reactions with D- and L-arginine, hydroxylating L-arginine at C3 and oxidatively deaminating D-arginine. Combining molecular dynamics with quantum mechanics/molecular mechanics (QM/MM) simulations, we reveal that the chirality of D-arginine positions its C2-H bond in proximity to the Fe(IV)-oxo intermediate and optimizes the geometry for enhanced σ-orbital alignment, thereby guiding the initial hydrogen atom transfer (HAT) from C2. Subsequent reactivity favors HAT from the ammonium group over alternative Glu-mediated proton coupled electron transfer pathway, driving C2-N desaturation to form a cationic imine intermediate. Both the C2-hydroxylation and C2-C3 desaturation pathways were ruled out due to their higher energy barriers. The cationi

SUBMITTER: Zhao C 

PROVIDER: S-EPMC12721151 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature