4c6v

Crystal structure of M. tuberculosis KasA in complex with TLM5 (Soak for 5 min)

spinqualitylabelsall models 4c6v, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4c6v is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: EDO, K, TLG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The survival of Mycobacterium tuberculosis depends on mycolic acids - very long alpha-alkyl-beta-hydroxy fatty acids comprising 60 to 90 carbon atoms. However, despite considerable efforts, little is known about how enzymes involved in mycolic acid biosynthesis recognize and bind their hydrophobic fatty acyl substrates. The condensing enzyme KasA is pivotal for the synthesis of very long (C38-42) fatty acids, the precursors of mycolic acids. To probe the mechanism of substrate and inhibitor recognition by KasA, we determined the structure of this protein in complex with a mycobacterial phospholipid, and with several thiolactomycin derivatives that were designed as substrate analogs. Our structures provide consecutive snapshots along the reaction coordinate for the enzyme-catalyzed reaction, and support an induced-fit mechanism in which a wide cavity is established through the concerted opening of three gatekeeping residues and several alpha-helices. The stepwise characterization of the binding process provides mechanistic insights into the induced-fit recognition in this system and serves as an excellent foundation for the development of high affinity KasA inhibitors. Structural Basis for the Recognition of Mycolic Acid Precursors by KasA, a Condensing Enzyme and Drug Target from Mycobacterium Tuberculosis.,Schiebel J, Kapilashrami K, Fekete A, Bommineni GR, Schaefer CM, Mueller MJ, Tonge PJ, Kisker C J Biol Chem. 2013 Oct 9. PMID:24108128 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acyl carrier protein synthase 3D structures

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