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-Structure paper
タイトル | Structure and conformational variability of the mycobacterium tuberculosis fatty acid synthase multienzyme complex. |
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ジャーナル・号・ページ | Structure, Vol. 21, Issue 7, Page 1251-1257, Year 2013 |
掲載日 | 2013年7月2日 |
著者 | Luciano Ciccarelli / Sean R Connell / Mathias Enderle / Deryck J Mills / Janet Vonck / Martin Grininger / |
PubMed 要旨 | 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 ...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. |
リンク | Structure / PubMed:23746808 |
手法 | EM (単粒子) |
解像度 | 17.5 - 27.0 Å |
構造データ | EMDB-2357, PDB-4v8w: EMDB-2358, PDB-4v8v: EMDB-2359: |
化合物 | ChemComp-FMN: |
由来 |
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キーワード | HYDROLASE / CODIMENSIONAL PRINCIPAL COMPONENT ANALYSIS / FATTY ACID SYNTHESIS / SAMPLE HETEROGENEITY / PROTEIN FLEXIBILITY |