TY  - JOUR
A1  - Willistein, Max
A1  - Bechtel, Dominique F.
A1  - Müller, Christina S.
A1  - Demmer, Ulrike
A1  - Heimann, Larissa
A1  - Kayastha, Kanwal
A1  - Schünemann, Volker
A1  - Pierik, Antonio J.
A1  - Ullmann, G. Matthias
A1  - Ermler, Ulrich
A1  - Boll, Matthias
T1  - Low potential enzymatic hydride transfer via highly cooperative and inversely functionalized flavin cofactors
T2  - Nature Communications
N2  - 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.
KW  - Biocatalysis
KW  - Enzyme mechanisms
KW  - X-ray crystallography
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50260
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-502607
SN  - 2041-1723
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
VL  - 10
IS  - 1, Art. 2074
SP  - 1
EP  - 10
PB  - Nature Publishing Group UK
CY  - [London]
ER  -