1jlr | pdb_00001jlr

STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE GTP COMPLEX 2 MUTANT C128V

spinqualitylabelsall models 1jlr, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1jlr is a 4 chain structure with sequence from Toxgo. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GTP, PO4 Related: 1bd3, 1bd4, 1upf, 1upu Activity: Uracil phosphoribosyltransferase, with EC number 2.4.2.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [UPP_TOXGO] Catalyzes the conversion of uracil and 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to UMP and diphosphate. 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 Uracil phosphoribosyltransferase (UPRT) is a member of a large family of salvage and biosynthetic enzymes, the phosphoribosyltransferases, and catalyzes the transfer of ribose 5-phosphate from alpha-d-5-phosphoribosyl-1-pyrophosphate (PRPP) to the N1 nitrogen of uracil. The UPRT from the opportunistic pathogen Toxoplasma gondii represents a promising target for rational drug design, because it can create intracellular, lethal nucleotides from subversive substrates. However, the development of such compounds requires a detailed understanding of the catalytic mechanism. Toward this end we determined the crystal structure of the T. gondii UPRT bound to uracil and cPRPP, a nonhydrolyzable PRPP analogue, to 2.5-A resolution. The structure suggests that the catalytic mechanism is substrate-assisted, and a tetramer would be the more active oligomeric form of the enzyme. Subsequent biochemical studies revealed that GTP binding, which has been suggested to play a role in catalysis by other UPRTs, causes a 6-fold activation of the T. gondii enzyme and strikingly stabilizes the tetramer form. The basis for stabilization was revealed in the 2.45-A resolution structure of the UPRT-GTP complex, whereby residues from three subunits contributed to GTP binding. Thus, our studies reveal an allosteric mechanism involving nucleotide stabilization of a more active, higher order oligomer. Such regulation of UPRT could play a role in the balance of purine and pyrimidine nucleotide pools in the cell. The structural mechanism of GTP stabilized oligomerization and catalytic activation of the Toxoplasma gondii uracil phosphoribosyltransferase.,Schumacher MA, Bashor CJ, Song MH, Otsu K, Zhu S, Parry RJ, Ullman B, Brennan RG Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):78-83. Epub 2002 Jan 2. PMID:11773618 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphoribosyltransferase

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