Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria
Xiaobo Chen, Jiayue Chen, Bing Yan, Wei Zhang, Luke W. Guddat, Xiang Liu, Zihe Rao
Abstract
Significance The lipid content accounts for approximately 60% of the dry weight of the cell wall of pathogenic mycobacteria with Mycobacterium tuberculosis having more than 250 genes involved in fatty acid metabolism. Previous studies have shown that acyl-CoA dehydrogenase (ACD), which introduces unsaturation into fatty acids, exhibits strict substrate specificity toward different CoA thioester groups. Here, we identified a unique ACD member in mycobacteria that exhibits broad substrate specificity. Furthermore, we determined crystal structures of the enzyme and enzyme–substrate complexes to explain the broad substrate recognition observed in this system. Given the importance of FadE5 in fatty acid metabolism, these new structures are excellent platforms for rational structure based antituberculosis drug discovery.