Low potential enzymatic hydride transfer via highly cooperative and inversely functionalized flavin cofactors.
Nat Commun
; 10(1): 2074, 2019 05 06.
Article
em En
| MEDLINE
| ID: mdl-31061390
ABSTRACT
Hydride transfers play a crucial role in a multitude of biological redox reactions and are mediated by flavin, deazaflavin or nicotinamide adenine dinucleotide cofactors at standard redox potentials ranging from 0 to -340 mV. 2-Naphthoyl-CoA reductase, a key enzyme of oxygen-independent bacterial naphthalene degradation, uses a low-potential one-electron donor for the two-electron dearomatization of its substrate below the redox limit of known biological hydride transfer processes at E°' = -493 mV. Here we demonstrate by X-ray structural analyses, QM/MM computational studies, and multiple spectroscopy/activity based titrations that highly cooperative electron transfer (n = 3) from a low-potential one-electron (FAD) to a two-electron (FMN) transferring flavin cofactor is the key to overcome the resonance stabilized aromatic system by hydride transfer in a highly hydrophobic pocket. The results evidence how the protein environment inversely functionalizes two flavins to switch from low-potential one-electron to hydride transfer at the thermodynamic limit of flavin redox chemistry.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oxirredutases
/
Proteínas de Bactérias
/
Modelos Moleculares
/
Coenzimas
/
Flavinas
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha