1upf
From Proteopedia
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| - | [[Image:1upf.jpg|left|200px]] | + | [[Image:1upf.jpg|left|200px]] |
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| - | '''STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE, MUTANT C128V BOUND TO THE DRUG 5-FLUOROURACIL''' | + | {{Structure |
| + | |PDB= 1upf |SIZE=350|CAPTION= <scene name='initialview01'>1upf</scene>, resolution 2.3Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=URF:5-FLUOROURACIL'>URF</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, MUTANT C128V BOUND TO THE DRUG 5-FLUOROURACIL''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UPF is a [ | + | 1UPF 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=1UPF OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding., Schumacher MA, Carter D, Scott DM, Roos DS, Ullman B, Brennan RG, EMBO J. 1998 Jun 15;17(12):3219-32. PMID:[http:// | + | Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding., Schumacher MA, Carter D, Scott DM, Roos DS, Ullman B, Brennan RG, EMBO J. 1998 Jun 15;17(12):3219-32. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9628859 9628859] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Toxoplasma gondii]] | [[Category: Toxoplasma gondii]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''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 14:35:06 2008'' |
Revision as of 12:35, 20 March 2008
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| , resolution 2.3Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Uracil phosphoribosyltransferase, with EC number 2.4.2.9 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE, MUTANT C128V BOUND TO THE DRUG 5-FLUOROURACIL
Overview
Uracil phosphoribosyltransferase (UPRTase) catalyzes the transfer of a ribosyl phosphate group from alpha-D-5-phosphoribosyl-1-pyrophosphate to the N1 nitrogen of uracil. The UPRTase from the opportunistic pathogen Toxoplasma gondii is a rational target for antiparasitic drug design. To aid in structure-based drug design studies against toxoplasmosis, the crystal structures of the T.gondii apo UPRTase (1.93 A resolution), the UPRTase bound to its substrate, uracil (2.2 A resolution), its product, UMP (2.5 A resolution), and the prodrug, 5-fluorouracil (2.3 A resolution), have been determined. These structures reveal that UPRTase recognizes uracil through polypeptide backbone hydrogen bonds to the uracil exocyclic O2 and endocyclic N3 atoms and a backbone-water-exocyclic O4 oxygen hydrogen bond. This stereochemical arrangement and the architecture of the uracil-binding pocket reveal why cytosine and pyrimidines with exocyclic substituents at ring position 5 larger than fluorine, including thymine, cannot bind to the enzyme. Strikingly, the T. gondii UPRTase contains a 22 residue insertion within the conserved PRTase fold that forms an extended antiparallel beta-arm. Leu92, at the tip of this arm, functions to cap the active site of its dimer mate, thereby inhibiting the escape of the substrate-binding water molecule.
About this Structure
1UPF is a Single protein structure of sequence from Toxoplasma gondii. Full crystallographic information is available from OCA.
Reference
Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding., Schumacher MA, Carter D, Scott DM, Roos DS, Ullman B, Brennan RG, EMBO J. 1998 Jun 15;17(12):3219-32. PMID:9628859
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