1jlr
From Proteopedia
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| - | [[Image:1jlr.gif|left|200px]] | + | [[Image:1jlr.gif|left|200px]] |
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| - | '''STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE GTP COMPLEX 2 MUTANT C128V''' | + | {{Structure |
| + | |PDB= 1jlr |SIZE=350|CAPTION= <scene name='initialview01'>1jlr</scene>, resolution 2.45Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene> and <scene name='pdbligand=GTP:GUANOSINE-5'-TRIPHOSPHATE'>GTP</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Uracil_phosphoribosyltransferase Uracil phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.9 2.4.2.9] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE GTP COMPLEX 2 MUTANT C128V''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1JLR is a [ | + | 1JLR is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JLR OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11773618 11773618] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Toxoplasma gondii]] | [[Category: Toxoplasma gondii]] | ||
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[[Category: uprtase]] | [[Category: uprtase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:05:09 2008'' |
Revision as of 10:05, 20 March 2008
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| , resolution 2.45Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Uracil phosphoribosyltransferase, with EC number 2.4.2.9 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
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