2pu0 | pdb_00002pu0

Crystal Structure of the T. brucei enolase complexed with phosphonoacetohydroxamate (PAH), His156-in conformation

spinqualitylabelsall models 2pu0, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2pu0 is a 1 chain structure with sequence from Trypanosoma brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, PAH, ZN Related: 1oep, 2ptw, 2ptx, 2pty, 2ptz Activity: Phosphopyruvate hydratase, with EC number 4.2.1.11 Resources: FirstGlance, OCA, RCSB, PDBsum 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 Enolase is a validated drug target in Trypanosoma brucei. To better characterize its properties and guide drug design efforts, we have determined six new crystal structures of the enzyme, in various ligation states and conformations, and have carried out complementary molecular dynamics simulations. The results show a striking structural diversity of loops near the catalytic site, for which variation can be interpreted as distinct modes of conformational variability that are explored during the molecular dynamics simulations. Our results show that sulfate may, unexpectedly, induce full closure of catalytic site loops whereas, conversely, binding of inhibitor phosphonoacetohydroxamate may leave open a tunnel from the catalytic site to protein surface offering possibilities for drug development. We also present the first complex of enolase with a novel inhibitor 2-fluoro-2-phosphonoacetohydroxamate. The molecular dynamics results further encourage efforts to design irreversible species-specific inhibitors: they reveal that a parasite enzyme-specific lysine may approach the catalytic site more closely than crystal structures suggest and also cast light on the issue of accessibility of parasite enzyme-specific cysteines to chemically modifying reagents. One of the new sulfate structures contains a novel metal-binding site IV within the catalytic site cleft. Structural flexibility in Trypanosoma brucei enolase revealed by X-ray crystallography and molecular dynamics.,de A S Navarro MV, Gomes Dias SM, Mello LV, da Silva Giotto MT, Gavalda S, Blonski C, Garratt RC, Rigden DJ FEBS J. 2007 Oct;274(19):5077-89. Epub 2007 Sep 5. PMID:17822439 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Enolase

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