Direct Proton-Coupled Electron Transfer between Interfacial Tyrosines in Ribonucleotide Reductase.

ABSTRACT: Ribonucleotide reductase (RNR) regulates DNA synthesis and repair in all organisms. The mechanism of Escherichia coli RNR requires radical transfer over a proton-coupled electron transfer (PCET) pathway spanning ∼32 Å across two protein subunits. A key step along this pathway is the interfacial PCET reaction between Y356 in the β subunit and Y731 in the α subunit. Herein, this PCET reaction between two tyrosines across an aqueous interface is explored with classical molecular dynamics and quantum mechanical/molecular mechanical (QM/MM) free energy simulations. The simulations suggest that the water-mediated mechanism involving double proton transfer through an intervening water molecule is thermodynamically and kinetically unfavorable. The direct PCET mechanism between Y356 and Y731

SUBMITTER: Zhong J 

PROVIDER: S-EPMC10344599 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature