Energetics and Dynamics of Proton-Coupled Electron Transfer in the NADH/FMN Site of Respiratory Complex I.
J Am Chem Soc
; 141(14): 5710-5719, 2019 04 10.
Article
em En
| MEDLINE
| ID: mdl-30873834
ABSTRACT
Complex I functions as an initial electron acceptor in aerobic respiratory chains that reduces quinone and pumps protons across a biological membrane. This remarkable charge transfer process extends ca. 300 Å and it is initiated by a poorly understood proton-coupled electron transfer (PCET) reaction between nicotinamide adenine dinucleotide (NADH) and a protein-bound flavin (FMN) cofactor. We combine here large-scale density functional theory calculations and quantum/classical models with atomistic molecular dynamics simulations to probe the energetics and dynamics of the NADH-driven PCET reaction in complex I. We find that the reaction takes place by concerted hydrogen atom (Hâ¢) transfer that couples to an electron transfer (eT) between the aromatic ring systems of the cofactors and further triggers reduction of the nearby FeS centers. In bacterial, Escherichia coli-like complex I isoforms, reduction of the N1a FeS center increases the binding affinity of the oxidized NAD+ that prevents the nucleotide from leaving prematurely. This electrostatic trapping could provide a protective gating mechanism against reactive oxygen species formation. We also find that proton transfer from the transient FMNH⢠to a nearby conserved glutamate (Glu97) residue favors eT from N1a onward along the FeS chain and modulates the binding of a new NADH molecule. The PCET in complex I isoforms with low-potential N1a centers is also discussed. On the basis of our combined results, we propose a putative mechanistic model for the NADH-driven proton/electron-transfer reaction in complex I.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Prótons
/
Complexo I de Transporte de Elétrons
/
Mononucleotídeo de Flavina
/
NAD
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article