Structure of Type-I Mycobacterium tuberculosis fatty acid synthase at 3.3 Å resolution.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30250274.
- Also identified by DOI 10.1038/s41467-018-06440-6 and PMC identifier 6155276.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 Å 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.
Medical subject headings
- Bacterial Proteins
- Drug Discovery
- Fatty Acid Synthases
- Mycobacterium tuberculosis