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==STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE, MUTANT C128V BOUND TO THE DRUG 5-FLUOROURACIL==
==STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE, MUTANT C128V BOUND TO THE DRUG 5-FLUOROURACIL==
<StructureSection load='1upf' size='340' side='right' caption='[[1upf]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
<StructureSection load='1upf' size='340' side='right'caption='[[1upf]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1upf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Toxgo Toxgo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UPF FirstGlance]. <br>
<table><tr><td colspan='2'>[[1upf]] is a 4 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UPF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=URF:5-FLUOROURACIL'>URF</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=URF:5-FLUOROURACIL'>URF</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1upf OCA], [http://pdbe.org/1upf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1upf RCSB], [http://www.ebi.ac.uk/pdbsum/1upf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1upf ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1upf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1upf OCA], [https://pdbe.org/1upf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1upf RCSB], [https://www.ebi.ac.uk/pdbsum/1upf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1upf ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/UPP_TOXGO UPP_TOXGO]] Catalyzes the conversion of uracil and 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to UMP and diphosphate.<ref>PMID:9247925</ref>
[https://www.uniprot.org/uniprot/UPP_TOXGO UPP_TOXGO] Catalyzes the conversion of uracil and 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to UMP and diphosphate.<ref>PMID:9247925</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1upf ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1upf ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
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<ref>PMID:9628859</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1upf" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Phosphoribosyltransferase|Phosphoribosyltransferase]]
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Toxgo]]
[[Category: Large Structures]]
[[Category: Uracil phosphoribosyltransferase]]
[[Category: Toxoplasma gondii]]
[[Category: Brennan, R G]]
[[Category: Brennan RG]]
[[Category: Carter, D]]
[[Category: Carter D]]
[[Category: Roos, D]]
[[Category: Roos D]]
[[Category: Schumacher, M A]]
[[Category: Schumacher MA]]
[[Category: Scott, D]]
[[Category: Scott D]]
[[Category: Ullman, B]]
[[Category: Ullman B]]
[[Category: Glycosyltransferase]]
[[Category: Phosphoribosyltransferase]]
[[Category: Transferase]]

Latest revision as of 11:45, 14 February 2024

STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE, MUTANT C128V BOUND TO THE DRUG 5-FLUOROURACILSTRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE, MUTANT C128V BOUND TO THE DRUG 5-FLUOROURACIL

Structural highlights

1upf is a 4 chain structure with sequence from Toxoplasma gondii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:,
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.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Carter D, Donald RG, Roos D, Ullman B. Expression, purification, and characterization of uracil phosphoribosyltransferase from Toxoplasma gondii. Mol Biochem Parasitol. 1997 Aug;87(2):137-44. PMID:9247925

1upf, resolution 2.30Å

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