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Low potential enzymatic hydride transfer via highly cooperative and inversely functionalized flavin cofactors.
- Source :
-
Nature communications [Nat Commun] 2019 May 06; Vol. 10 (1), pp. 2074. Date of Electronic Publication: 2019 May 06. - Publication Year :
- 2019
-
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.
- Subjects :
- Bacterial Proteins isolation & purification
Bacterial Proteins metabolism
Coenzymes metabolism
Computer Simulation
Crystallography, X-Ray
Electron Transport
Flavins metabolism
Naphthalenes chemistry
Naphthalenes metabolism
Oxidoreductases isolation & purification
Oxidoreductases metabolism
Protein Structure, Tertiary
Recombinant Proteins chemistry
Recombinant Proteins isolation & purification
Recombinant Proteins metabolism
Spectrum Analysis
Bacterial Proteins chemistry
Coenzymes chemistry
Flavins chemistry
Models, Molecular
Oxidoreductases chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31061390
- Full Text :
- https://doi.org/10.1038/s41467-019-10078-3