1upf

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(New page: 200px<br /><applet load="1upf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1upf, resolution 2.3&Aring;" /> '''STRUCTURE OF THE URAC...)
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[[Image:1upf.jpg|left|200px]]<br /><applet load="1upf" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1upf, resolution 2.3&Aring;" />
 
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'''STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE, MUTANT C128V BOUND TO THE DRUG 5-FLUOROURACIL'''<br />
 
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==Overview==
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==STRUCTURE OF THE URACIL PHOSPHORIBOSYLTRANSFERASE, MUTANT C128V BOUND TO THE DRUG 5-FLUOROURACIL==
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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.
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<StructureSection load='1upf' size='340' side='right'caption='[[1upf]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<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>
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</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>
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<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>
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<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>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/up/1upf_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1UPF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Toxoplasma_gondii Toxoplasma gondii] with SO4 and URF as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UPF OCA].
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*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
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== References ==
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==Reference==
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<references/>
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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://ispc.weizmann.ac.il//pmbin/getpm?pmid=9628859 9628859]
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__TOC__
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[[Category: Single protein]]
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Toxoplasma gondii]]
[[Category: Toxoplasma gondii]]
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[[Category: Uracil phosphoribosyltransferase]]
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[[Category: Brennan RG]]
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[[Category: Brennan, R.G.]]
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[[Category: Carter D]]
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[[Category: Carter, D.]]
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[[Category: Roos D]]
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[[Category: Roos, D.]]
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[[Category: Schumacher MA]]
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[[Category: Schumacher, M.A.]]
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[[Category: Scott D]]
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[[Category: Scott, D.]]
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[[Category: Ullman B]]
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[[Category: Ullman, B.]]
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[[Category: SO4]]
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[[Category: URF]]
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[[Category: glycosyltransferase]]
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[[Category: phosphoribosyltransferase]]
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[[Category: transferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 04:17:09 2007''
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Current revision

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

PDB ID 1upf

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