Structure of Type-I Mycobacterium tuberculosis fatty acid synthase at 3.3 angstrom resolution

Nadav Elad, Szilvia Baron, Yoav Peleg, Shira Albeck, Jacob Grunwald, Gal Raviv, Zippora Shakked, Oren Zimhony, Ron Diskin

Research output: Contribution to journalArticlepeer-review

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 multidrug 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 angstrom resolution structure of the similar to 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.

Original languageEnglish
Article number3886
Number of pages6
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 24 Sep 2018

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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