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

ABSTRACT: 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, ?-FAD (bound to domain II of EtfA) and ?-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, ?-FAD and ?-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 ?-FAD, which bifurcates. One electron goes to ferredoxin and one to ?-FAD, which swings over to reduce ?-FAD to the semiquinone. Repetition affords a second reduced ferredoxin and ?-FADH-, which reduces crotonyl-CoA.

SUBMITTER: Demmer JK 

PROVIDER: S-EPMC5691135 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature