The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile

  • The electron transferring flavoprotein/butyryl-CoA dehydrogenase (EtfAB/Bcd) catalyzes the reduction of one crotonyl-CoA and two ferredoxins by two NADH within a flavin-based electron-bifurcating process. Here we report on the X-ray structure of the Clostridium difficile (EtfAB/Bcd)4 complex in the dehydrogenase-conducting D-state, α-FAD (bound to domain II of EtfA) and δ-FAD (bound to Bcd) being 8 Å apart. Superimposing Acidaminococcus fermentans EtfAB onto C. difficile EtfAB/Bcd reveals a rotation of domain II of nearly 80°. Further rotation by 10° brings EtfAB into the bifurcating B-state, α-FAD and β-FAD (bound to EtfB) being 14 Å apart. This dual binding mode of domain II, substantiated by mutational studies, resembles findings in non-bifurcating EtfAB/acyl-CoA dehydrogenase complexes. In our proposed mechanism, NADH reduces β-FAD, which bifurcates. One electron goes to ferredoxin and one to α-FAD, which swings over to reduce δ-FAD to the semiquinone. Repetition affords a second reduced ferredoxin and δ-FADH−, which reduces crotonyl-CoA.
Author:Julius Konstantin Demmer, Nilanjan Pal ChowdhuryORCiDGND, Thorsten Selmer, Ulrich Ermler, Wolfgang BuckelORCiDGND
Pubmed Id:
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Year of Completion:2017
Date of first Publication:2017/11/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/09/20
Tag:Cellular microbiology; Enzyme mechanisms
Issue:1, Art. 1577
Page Number:10
First Page:1
Last Page:10
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Institutes: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