4V8W

Structure and conformational variability of the Mycobacterium tuberculosis fatty acid synthase multienzyme complex

This is a non-PDB format compatible entry.

Summary for 4V8W

• Entry DOI: 10.2210/pdb4v8w/pdb
• Related: 4BJD 4BJE
• EMDB information: 2357
• Descriptor: TYPE-I FATTY ACID SYNTHASE, FLAVIN MONONUCLEOTIDE (2 entities in total)
• Functional Keywords: hydrolase, fatty acid synthesis, sample heterogeneity, protein flexibility, codimensional principal component analysis
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Total number of polymer chains: 6
• Total formula weight: 1982065.88

Authors

Ciccarelli, L.,Connell, S.R.,Enderle, M.,Mills, D.J.,Vonck, J.,Grininger, M. (deposition date: 2013-04-18, release date: 2014-07-09, Last modification date: 2024-05-08)

Primary citation

Ciccarelli, L.,Connell, S.R.,Enderle, M.,Mills, D.J.,Vonck, J.,Grininger, M.
Structure and Conformational Variability of the Mycobacterium Tuberculosis Fatty Acid Synthase Multienzyme Complex.
Structure, 21:1251-, 2013

PubMed Abstract: Antibiotic therapy in response to Mycobacterium tuberculosis infections targets de novo fatty acid biosynthesis, which is orchestrated by a 1.9 MDa type I fatty acid synthase (FAS). Here, we characterize M. tuberculosis FAS by single-particle cryo-electron microscopy and interpret the data by docking the molecular models of yeast and Mycobacterium smegmatis FAS. Our analysis reveals a porous barrel-like structure of considerable conformational variability that is illustrated by the identification of several conformational states with altered topology in the multienzymatic assembly. This demonstrates that the barrel-like structure of M. tuberculosis FAS is not just a static scaffold for the catalytic domains, but may play an active role in coordinating fatty acid synthesis. The conception of M. tuberculosis FAS as a highly dynamic assembly of domains revises the view on bacterial type I fatty acid synthesis and might inspire new strategies for inhibition of de novo fatty acid synthesis in M. tuberculosis.

PubMed: 23746808
DOI: 10.1016/J.STR.2013.04.023

Experimental method

ELECTRON MICROSCOPY (17.5 Å)