1kie | pdb_00001kie

Inosine-adenosine-guanosine preferring nucleoside hydrolase from Trypanosoma vivax: Asp10Ala mutant in complex with 3-deaza-adenosine

spinqualitylabelsall models 1kie, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1kie is a 2 chain structure with sequence from Trypanosoma vivax. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: AD3, CA, NI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9GPQ4_TRYVI 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 Nucleoside hydrolases are key enzymes in the purine salvage pathway of Trypanosomatidae and are considered as targets for drug design. We previously reported the first x-ray structure of an inosine-adenosine-guanosine preferring nucleoside hydrolase (IAG-NH) from Trypanosoma vivax (). Here we report the 2.0-A crystal structure of the slow D10A mutant in complex with the inhibitor 3-deaza-adenosine and the 1.6-A crystal structure of the same enzyme in complex with a genuine substrate inosine. The enzyme-substrate complex shows the substrate bound to the enzyme in a different conformation from 3-deaza-adenosine and provides a snapshot along the reaction coordinate of the enzyme-catalyzed reaction. The chemical groups on the substrate important for binding and catalysis are mapped. The 2'-OH, 3'-OH, and 5'-OH contribute 4.6, 7.5, and 5.4 kcal/mol to k(cat)/K(m), respectively. Specific interactions with the exocyclic groups on the purine ring are not required for catalysis. Site-directed mutagenesis indicates that the purine specificity of the IAG-NHs is imposed by a parallel aromatic stacking interaction involving Trp(83) and Trp(260). The pH profiles of k(cat) and k(cat)/K(m) indicate the existence of one or more proton donors, possibly involved in leaving group activation. However, mutagenesis of the active site residues around the nucleoside base and an alanine scan of a flexible loop near the active site fail to identify this general acid. The parallel aromatic stacking seems to provide the most likely alternative mechanism for leaving group activation. Enzyme-substrate interactions in the purine-specific nucleoside hydrolase from Trypanosoma vivax.,Versees W, Decanniere K, Van Holsbeke E, Devroede N, Steyaert J J Biol Chem. 2002 May 3;277(18):15938-46. Epub 2002 Feb 19. PMID:11854281 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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