The structure of glucose-1-phosphate thymidylyltransferase from Mycobacterium tuberculosis reveals the location of an essential magnesium ion in the RmlA-type enzymes.

ABSTRACT: Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, continues to be a major threat to populations worldwide. Whereas the disease is treatable, the drug regimen is arduous at best with the use of four antimicrobials over a six-month period. There is clearly a pressing need for the development of new therapeutics. One potential target for structure-based drug design is the enzyme RmlA, a glucose-1-phosphate thymidylyltransferase. This enzyme catalyzes the first step in the biosynthesis of l-rhamnose, which is a deoxysugar critical for the integrity of the bacterium's cell wall. Here, we report the X-ray structures of M. tuberculosis RmlA in complex with either dTTP or dTDP-glucose to 1.6 Å and 1.85 Å resolution, respectively. In the RmlA/dTTP complex, two magnesium ions were ob

SUBMITTER: Brown HA 

PROVIDER: S-EPMC5775166 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature