Direct Proton-Coupled Electron Transfer between Interfacial Tyrosines in Ribonucleotide Reductase.
J Am Chem Soc
; 145(8): 4784-4790, 2023 03 01.
Article
em En
| MEDLINE
| ID: mdl-36802630
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 â¼32 Å across two protein subunits. A key step along this pathway is the interfacial PCET reaction between Y356 in the ß 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 becomes feasible when Y731 is flipped toward the interface and is predicted to be approximately isoergic with a relatively low free energy barrier. This direct mechanism is facilitated by the hydrogen bonding of water to both Y356 and Y731. These simulations provide fundamental insights into radical transfer across aqueous interfaces.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ribonucleotídeo Redutases
/
Tirosina
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos