1kph | pdb_00001kph

Crystal Structure of mycolic acid cyclopropane synthase CmaA1 complexed with SAH and DDDMAB

spinqualitylabelsall models 1kph, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1kph is a 4 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 10A, CO3, SAH Related: 1kp9, 1kpg, 1kpi Gene: cmaA1 (Mycobacterium tuberculosis) Activity: Cyclopropane-fatty-acyl-phospholipid synthase, with EC number 2.1.1.79 Resources: FirstGlance, OCA, RCSB, PDBsum, TOPSAN Function [CMAS1_MYCTU] Catalyzes the conversion of a double bond to a cyclopropane ring at the distal position of an alpha mycolic acid via the transfer of a methylene group from S-adenosyl-L-methionine. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Mycolic acids are major components of the cell wall of Mycobacterium tuberculosis. Several studies indicate that functional groups in the acyl chain of mycolic acids are important for pathogenesis and persistence. There are at least three mycolic acid cyclopropane synthases (PcaA, CmaA1, and CmaA2) that are responsible for these site-specific modifications of mycolic acids. To derive information on the specificity and enzyme mechanism of the family of proteins, the crystal structures of CmaA1, CmaA2, and PcaA were solved to 2-, 2-, and 2.65-A resolution, respectively. All three enzymes have a seven-stranded alpha/beta fold similar to other methyltransferases with the location and interactions with the cofactor S-adenosyl-l-methionine conserved. The structures of the ternary complexes demonstrate the position of the mycolic acid substrate binding site. Close examination of the active site reveals electron density that we believe represents a bicarbonate ion. The structures support the hypothesis that these enzymes catalyze methyl transfer via a carbocation mechanism in which the bicarbonate ion acts as a general base. In addition, comparison of the enzyme structures reveals a possible mechanism for substrate specificity. These structures provide a foundation for rational-drug design, which may lead to the development of new inhibitors effective against persistent bacteria. Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis.,Huang CC, Smith CV, Glickman MS, Jacobs WR Jr, Sacchettini JC J Biol Chem. 2002 Mar 29;277(13):11559-69. Epub 2001 Dec 26. PMID:11756461 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Fatty acid synthase

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