title: Electron and Hydrogen Atom Transfers in the Hydride Carrier Protein EmoB.
abstract: In this article, we investigate the mechanism of hydride transfer taking place within the EmoB protein of the Mesorhizobium species. The reaction involves the net transfer of one proton and two electrons from a reduced flavin mononucleotide (FMN) cofactor, which is anchored in the protein scaffold, to a diffusible oxidized FMN cofactor, both being held together by π-stacking interactions. To analyze the formal hydride transfer in terms of more elementary steps, electron transfer (ET), and hydrogen atom transfers (HAT), we employ a combination of classical molecular dynamics simulations and hybrid constrained Density Functional Theory/Molecular Mechanics (cDFT/MM) energy calculations to build the free energy profiles, for the ET before and after HAT occurs between the flavins. The main outcomes of our study are first to highlight the role of the protein in stabilizing the π-stacked FMN dimer and second to reveal the coupling between the ET and HAT. Before HAT has taken place, ET is unfavorable by 8 kcal/mol and become favorable by 8 kcal/mol after HAT. Our simulations show that such a coupling is not present for the analogous process in water (ET is almost athermal). This suggests a functional role for the protein matrix to ensure EmoB a role of hydride carrier in the Mesorhizobium species.
authors.affiliation: Laboratoire de Chimie-Physique, Université Paris Sud , CNRS, UMR 8000, 15 rue Jean Perrin, 91405 Orsay CEDEX, France.|Departament de Química Física i Analítica, Universitat Jaume I , 12071 Castellón, Spain.
authors.forename: Natacha
authors.initials: N
authors.lastname: Gillet
authors.affiliation: Laboratoire de Chimie-Physique, Université Paris Sud , CNRS, UMR 8000, 15 rue Jean Perrin, 91405 Orsay CEDEX, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lévy
authors.affiliation: Departament de Química Física i Analítica, Universitat Jaume I , 12071 Castellón, Spain.
authors.forename: Vicent
authors.initials: V
authors.lastname: Moliner
authors.affiliation: Laboratoire de Chimie-Physique, Université Paris Sud , CNRS, UMR 8000, 15 rue Jean Perrin, 91405 Orsay CEDEX, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Demachy
authors.affiliation: Laboratoire de Chimie-Physique, Université Paris Sud , CNRS, UMR 8000, 15 rue Jean Perrin, 91405 Orsay CEDEX, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: de la Lande