Crystal structure of the S-Adenosylmethionine-dependent mycolic acid synthase UmaA from Mycobacterium tuberculosis

Mycobacterium tuberculosis is a Gram-positive bacillus that causes tuberculosis and is a leading cause of mortality worldwide. This disease is a growing health threat due to the occurrence of multidrug resistance. Mycolic acids are essential for generating cell walls and their modification is important to the virulence and persistence of M.Tuberculosis. A family of S-Adenosylmethionine-dependent mycolic acid synthases modify mycolic acids and represent promising drug targets. UmaA is currently the least-understood member of this family. This paper describes the crystal structure of UmaA. UmaA is a monomer composed of two domains: A structurally conserved SAM-binding domain and a variable substrate-binding auxiliary domain. Fortuitously, our structure contains a nitrate in the active site, a structural mimic of carbonate, which is a known general base in cyclopropane-Adding synthases. Further investigation indicated that the structure of the N-Terminus is highly flexible. Finally, we have identified S-Adenosyl-N-decyl-Aminoethyl as a promising potential inhibitor.