Architecture of the mycobacterial succinate dehydrogenase with a membrane-embedded Rieske FeS cluster
Xiaoting Zhou, Yan Gao, Weiwei Wang, Xiaolin Yang, Xiuna Yang, Fengjiang Liu, Yanting Tang, Sin Man Lam, Guanghou Shui, Lu Yu, Changlin Tian, Luke W. Guddat, Quan Wang, Zihe Rao, Hongri Gong
Abstract
Significance Targeting energy metabolism in Mycobacterium tuberculosis has emerged as a new paradigm in antituberculosis drug discovery. Succinate dehydrogenase is considered the regulator of respiration in M. tuberculosis . Mycobacteria contains two different succinate dehydrogenase enzymes designated Sdh1 and Sdh2. Sdh1 has recently been identified as a new class of succinate dehydrogenase. In this study, we have determined M. smegmatis Sdh1 structures alone and in the presence of ubiquinone-1, revealing that Sdh1 has a novel electron transfer pathway and a unique substrate-binding site. These data show that the structure of M. tuberculosis Sdh1 is significantly different by comparison with the human counterpart making a good antituberculosis drug target.