1jlr
From Proteopedia
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STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE GTP COMPLEX 2 MUTANT C128V
Overview
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.
About this Structure
1JLR is a Single protein structure of sequence from Toxoplasma gondii with PO4 and GTP as ligands. Active as Uracil phosphoribosyltransferase, with EC number 2.4.2.9 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Tue Nov 20 18:22:11 2007
