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

• DOI: 10.1021/jacs.2c13615
• Publication Date: 2023-02-20T21:17:29Z
• Authors: Jiayun Zhong; Clorice R. Reinhardt; Sharon Hammes-Sch...
• Keywords: Ribonucleotide reductase; Proton-Coupled Electron Transfer; Ribonucleotide

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 (PCET) pathway spanning ∼32 Å across two protein subunits. A key step along this is the interfacial PCET reaction between Y356 β subunit Y731 α subunit. Herein, tyrosines an aqueous interface explored with classical molecular dynamics quantum mechanical/molecular mechanical (QM/MM) free energy simulations. simulations suggest that water-mediated involving double proton through intervening water molecule thermodynamically kinetically unfavorable. direct becomes feasible when flipped toward predicted to be approximately isoergic relatively low barrier. This facilitated by hydrogen bonding both Y731. These provide fundamental insights into interfaces.