2tsr: Difference between revisions

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[[Image:2tsr.gif|left|200px]]<br />
<applet load="2tsr" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2tsr, resolution 2.60&Aring;" />
'''THYMIDYLATE SYNTHASE FROM RAT IN TERNARY COMPLEX WITH DUMP AND TOMUDEX'''<br />


==Overview==
==THYMIDYLATE SYNTHASE FROM RAT IN TERNARY COMPLEX WITH DUMP AND TOMUDEX==
Two crystal structures of rat thymidylate synthase (TS) complexed with, dUMP and the anticancer drug Tomudex (ZD1694) have been determined to, resolutions of 3.3 and 2.6 A. Tomudex is one of several new antifolates, targeted to TS and the first to be approved for clinical use. The, structures represent the first views of any mammalian TS bound to ligands, and suggest that the rat protein undergoes a ligand-induced conformational, change similar to that of the Escherichia coli protein. Surprisingly, Tomudex does not induce the "closed" conformation in rat TS that is seen, on binding to E. coli TS, resulting in inhibitor atoms that differ in, position by more than 1.5 A. Several species-specific differences in, sequence may be the reason for this. Phe 74 shifts to a new position in, the rat ... [[http://ispc.weizmann.ac.il/pmbin/getpm?9894005 (full description)]]
<StructureSection load='2tsr' size='340' side='right'caption='[[2tsr]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2tsr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2TSR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2TSR 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D16:TOMUDEX'>D16</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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=2tsr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2tsr OCA], [https://pdbe.org/2tsr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2tsr RCSB], [https://www.ebi.ac.uk/pdbsum/2tsr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2tsr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TYSY_RAT TYSY_RAT] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway (By similarity).
== 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/ts/2tsr_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=2tsr ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2TSR is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]] with UMP and D16 as [[http://en.wikipedia.org/wiki/ligands ligands]]. Active as [[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase]], with EC number [[http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45]]. Structure known Active Site: NUL. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2TSR OCA]].
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Crystal structures of rat thymidylate synthase inhibited by Tomudex, a potent anticancer drug., Sotelo-Mundo RR, Ciesla J, Dzik JM, Rode W, Maley F, Maley GF, Hardy LW, Montfort WR, Biochemistry. 1999 Jan 19;38(3):1087-94. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9894005 9894005]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: Ciesla J]]
[[Category: Thymidylate synthase]]
[[Category: Dzik JM]]
[[Category: Ciesla, J.]]
[[Category: Hardy LW]]
[[Category: Dzik, J.M.]]
[[Category: Maley F]]
[[Category: Hardy, L.W.]]
[[Category: Maley G]]
[[Category: Maley, F.]]
[[Category: Montfort WR]]
[[Category: Maley, G.]]
[[Category: Rode W]]
[[Category: Montfort, W.R.]]
[[Category: Sotelo-Mundo RR]]
[[Category: Rode, W.]]
[[Category: Sotelo-Mundo, R.R.]]
[[Category: D16]]
[[Category: UMP]]
[[Category: antifolate]]
[[Category: dump]]
[[Category: methyltransferase]]
[[Category: thymidylate synthase]]
[[Category: tomudex]]
 
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