1sux

CRYSTALLOGRAPHIC ANALYSIS OF THE COMPLEX BETWEEN TRIOSEPHOSPHATE ISOMERASE FROM TRYPANOSOMA CRUZI AND 3-(2-benzothiazolylthio)-1-propanesulfonic acid

spinqualitylabelsall models 1sux, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1sux is a 2 chain structure with sequence from Trypanosoma cruzi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: BTS, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TPIS_TRYCR 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 We characterized by crystallographic, calorimetric and biochemical methods the action of a low molecular weight compound, 3-(2-benzothiazolylthio)-1-propanesulfonic acid (compound 8) that binds to the dimer interface of triosephosphate isomerase from Trypanosoma cruzi (TcTIM) and thereby abolishes its function with a high level of selectivity. The kinetics of TcTIM inactivation by the agent and isothermal titration calorimetry experiments showed that the binding of two molecules of the compound per enzyme is needed for inactivation. The binding of the first molecule is endothermic, and that of the second exothermic. Crystals of TcTIM in complex with one molecule of the inactivating agent that diffracted to a resolution of 2A were obtained. The compound is at the dimer interface at less than 4A from residues of the two subunits. Compound 8 is more effective at low than at high protein concentrations, indicating that it perturbs the association between the two TcTIM monomers. Calorimetric and kinetic data of experiments in which TcTIM was added to a solution of the inactivating agent showed that at low concentrations of the compound, inactivation is limited by binding, whereas at high concentrations of the agent, the events that follow binding become rate-limiting. The portion of the interface of TcTIM that binds the benzothiazole derivative and its equivalent region in human TIM differs in amino acid composition and hydrophobic packing. Thus, we show that by focusing on protein-protein interfaces, it is possible to discover low molecular weight compounds that are selective for enzymes from parasites. Inactivation of triosephosphate isomerase from Trypanosoma cruzi by an agent that perturbs its dimer interface.,Tellez-Valencia A, Olivares-Illana V, Hernandez-Santoyo A, Perez-Montfort R, Costas M, Rodriguez-Romero A, Lopez-Calahorra F, Tuena De Gomez-Puyou M, Gomez-Puyou A J Mol Biol. 2004 Aug 27;341(5):1355-65. PMID:15321726 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Triose phosphate isomerase 3D structures

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