View source for 1uou


==Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor==
<StructureSection load='1uou' size='340' side='right'caption='[[1uou]], [[Resolution|resolution]] 2.11&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1uou]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UOU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UOU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.11&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMU:5-CHLORO-6-(1-(2-IMINOPYRROLIDINYL)+METHYL)+URACIL'>CMU</scene></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=1uou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uou OCA], [https://pdbe.org/1uou PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uou RCSB], [https://www.ebi.ac.uk/pdbsum/1uou PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uou ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TYPH_HUMAN TYPH_HUMAN] Mitochondrial neurogastrointestinal encephalomyopathy. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:9924029</ref> <ref>PMID:12177387</ref> 
== Function ==
[https://www.uniprot.org/uniprot/TYPH_HUMAN TYPH_HUMAN] May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro.<ref>PMID:1590793</ref>   Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.<ref>PMID:1590793</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uo/1uou_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1uou ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human thymidine phosphorylase (HTP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is overexpressed in certain solid tumors where it is linked to poor prognosis. HTP expression is utilized for certain chemotherapeutic strategies and is also thought to play a role in tumor angiogenesis. We determined the structure of HTP bound to the small molecule inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI). The inhibitor appears to mimic the substrate transition state, which may help explain the potency of this inhibitor and the catalytic mechanism of pyrimidine nucleotide phosphorylases (PYNPs). Further, we have confirmed the validity of the HTP structure as a template for structure-based drug design by predicting binding affinities for TPI and other known HTP inhibitors using in silico docking techniques. This work provides the first structural insight into the binding mode of any inhibitor to this important drug target and forms the basis for designing novel inhibitors for use in anticancer therapy.

Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor.,Norman RA, Barry ST, Bate M, Breed J, Colls JG, Ernill RJ, Luke RW, Minshull CA, McAlister MS, McCall EJ, McMiken HH, Paterson DS, Timms D, Tucker JA, Pauptit RA Structure. 2004 Jan;12(1):75-84. PMID:14725767<ref>PMID:14725767</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1uou" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Barry ST]]
[[Category: Bate M]]
[[Category: Breed J]]
[[Category: Colls JG]]
[[Category: Ernill RJ]]
[[Category: Luke RWA]]
[[Category: McAlister MSB]]
[[Category: McCall EJ]]
[[Category: McMiken HHJ]]
[[Category: Minshull CA]]
[[Category: Norman RA]]
[[Category: Paterson DS]]
[[Category: Pauptit RA]]
[[Category: Timms D]]
[[Category: Tucker JA]]