Tuberculosis (TB) is a devastating and rapidly spreading disease caused by Mycobacterium tuberculosis (Mtb). Therapy requires prolonged treatment with a combination of multiple agents and interruptions in the treatment regimen result in emergence and spread of multi-drug resistant (MDR) Mtb strains. MDR Mtb poses a significant global health problem, calling for urgent development of novel drugs to combat TB. Here, we report the 3.3 A resolution structure of the ~2 MDa type-I fatty acid synthase (FAS-I) from Mtb, determined by single particle cryo-EM. Mtb FAS-I is an essential enzymatic complex that contributes to the virulence of Mtb, and thus a prime target for anti-TB drugs. The structural information for Mtb FAS-I we have obtained enables computer-based drug discovery approaches, and the resolution achieved by cryo-EM is sufficient for elucidating inhibition mechanisms by putative small molecular weight inhibitors.
Structure of Type-I Mycobacterium tuberculosis fatty acid synthase at 3.3 A resolution.,Elad N, Baron S, Peleg Y, Albeck S, Grunwald J, Raviv G, Shakked Z, Zimhony O, Diskin R Nat Commun. 2018 Sep 24;9(1):3886. doi: 10.1038/s41467-018-06440-6. PMID:30250274[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
