3ble | pdb_00003ble

Crystal structure of the catalytic domain of LiCMS in complexed with malonate

spinqualitylabelsall models 3ble, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ble is a 1 chain structure with sequence from "leptospira_icteroides"_noguchi_1919 "leptospira icteroides" noguchi 1919. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MLI, ZN Related: 3blf, 3bli Gene: cimA ("Leptospira icteroides" Noguchi 1919) Activity: 2-isopropylmalate synthase, with EC number 2.3.3.13 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 Leptospira interrogans is the causative agent for leptospirosis, a zoonotic disease of global importance. In contrast with most other micro-organisms, L. interrogans employs a pyruvate pathway to synthesize isoleucine and LiCMS (L. interrogans citramalate synthase) catalyses the first reaction of the pathway which converts pyruvate and acetyl-CoA into citramalate, thus making it an attractive target for the development of antibacterial agents. We report here the crystal structures of the catalytic domain of LiCMS and its complexes with substrates, and kinetic and mutagenesis studies of LiCMS, which together reveal the molecular basis of the high substrate specificity and the catalytic mechanism of LiCMS. The catalytic domain consists of a TIM barrel flanked by an extended C-terminal region. It forms a homodimer in the crystal structure, and the active site is located at the centre of the TIM barrel near the C-terminal ends of the beta-strands and is composed of conserved residues of the beta-strands of one subunit and the C-terminal region of the other. The substrate specificity of LiCMS towards pyruvate against other alpha-oxo acids is dictated primarily by residues Leu(81), Leu(104) and Tyr(144), which form a hydrophobic pocket to accommodate the C(2)-methyl group of pyruvate. The catalysis follows the typical aldol condensation reaction, in which Glu(146) functions as a catalytic base to activate the methyl group of acetyl-CoA to form an enolated acetyl-CoA intermediate and Arg(16) as a general acid to stabilize the intermediate. Molecular basis of the substrate specificity and the catalytic mechanism of citramalate synthase from Leptospira interrogans.,Ma J, Zhang P, Zhang Z, Zha M, Xu H, Zhao G, Ding J Biochem J. 2008 Oct 1;415(1):45-56. PMID:18498255 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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