Solvent Channels and Electric Fields Guide Proton Delivery to the Active Site of Heme Peroxidases.

ABSTRACT: The active sites of heme enzymes have evolved to control the formation of highly reactive intermediates in oxidative catalysis. Proton delivery to the heme is essential, yet the mechanisms of proton delivery remain poorly understood. Here, we identify routes and drivers of proton delivery in a heme peroxidase (ascorbate peroxidase) using computational approaches that combine classical, quantum, and hybrid methods with enhanced sampling and local electric field (LEF) analyses. Our results show that networks of active-site water molecules facilitate proton exchange with Arg38, which may act as a transient proton carrier at the γ-heme edge where the substrate binds. The distal His42 residue aids proton transfer into the active site via solvent at the δ-edge. Molecular dynamics simulations of

SUBMITTER: Suardiaz R 

PROVIDER: S-EPMC12684355 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature