4tim

CRYSTALLOGRAPHIC AND MOLECULAR MODELING STUDIES ON TRYPANOSOMAL TRIOSEPHOSPHATE ISOMERASE: A CRITICAL ASSESSMENT OF THE PREDICTED AND OBSERVED STRUCTURES OF THE COMPLEX WITH 2-PHOSPHOGLYCERATECRYSTALLOGRAPHIC AND MOLECULAR MODELING STUDIES ON TRYPANOSOMAL TRIOSEPHOSPHATE ISOMERASE: A CRITICAL ASSESSMENT OF THE PREDICTED AND OBSERVED STRUCTURES OF THE COMPLEX WITH 2-PHOSPHOGLYCERATE

Structural highlights 4tim is a 2 chain structure with sequence from Trypanosoma brucei brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Activity: Triose-phosphate isomerase, with EC number 5.3.1.1 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 In the continuation of a project aimed at the rational design of drugs against diseases caused by trypanosomes, the crystal structure of trypanosomal triosephosphate isomerase in complex with the active site inhibitor 2-phosphoglycerate has been determined. Two alternative modeling protocols have been attempted to predict the mode of binding of this ligand. In the first protocol, certain key interactions were restrained in the modeling procedure. In the second protocol, a full search of ligand conformational space was performed. In both cases the protein scaffold was kept static. Both protocols produced models which were reasonably close to the observed structure (rms difference less than 2.0 A). Nevertheless, some essential features were missed by each of the protocols. The crystallographic structure of the 2-PGA TIM complex shows that the ligand binds fully within the active site of TIM, with partners for all but one of the ligand's strongly hydrogen bonding groups. Several of the interactions between the ligand and the active site of TIM are seen to be common to all of the complexes so far structurally characterized between trypanosomal triosephosphate isomerase and competitive inhibitors. Such key interactions appear to be the best guide in the prediction of the binding mode of a new inhibitor. Crystallographic and molecular modeling studies on trypanosomal triosephosphate isomerase: a critical assessment of the predicted and observed structures of the complex with 2-phosphoglycerate.,Noble ME, Verlinde CL, Groendijk H, Kalk KH, Wierenga RK, Hol WG J Med Chem. 1991 Sep;34(9):2709-18. PMID:1895291 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Triose Phosphate Isomerase

spinqualitylabelsall models 4tim, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image