Low potential enzymatic hydride transfer via highly cooperative and inversely functionalized flavin cofactors

  • 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.
Author:Max Willistein, Dominique F. Bechtel, Christina S. Müller, Ulrike Demmer, Larissa Heimann, Kanwal Kayastha, Volker Schünemann, Antonio J. Pierik, G. Matthias Ullmann, Ulrich Ermler, Matthias Boll
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31061390
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/05/06
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/05/16
Tag:Biocatalysis; Enzyme mechanisms; X-ray crystallography
Issue:1, Art. 2074
Page Number:10
First Page:1
Last Page:10
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Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Angeschlossene und kooperierende Institutionen / MPI für Biophysik
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung 4.0