View source for 2rda


==Human Thymidylate Synthase Stabilized in Active Conformation by R163K Mutation: Asymmetry and Reactivity of Cys195==
<StructureSection load='2rda' size='340' side='right'caption='[[2rda]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2rda]] is a 6 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=2RDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RDA 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]] 2.67&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=2rda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rda OCA], [https://pdbe.org/2rda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rda RCSB], [https://www.ebi.ac.uk/pdbsum/2rda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rda ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</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/rd/2rda_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=2rda ConSurf].
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== Publication Abstract from PubMed ==
Loop 181-197 of human thymidylate synthase (hTS) populates two conformational states. In the first state, Cys195, a residue crucial for catalytic activity, is in the active site (active conformer); in the other conformation, it is about 10 A away, outside the active site (inactive conformer). We have designed and expressed an hTS variant, R163K, in which the inactive conformation is destabilized. The activity of this mutant is 33% higher than that of wt hTS, suggesting that at least one-third of hTS populates the inactive conformer. Crystal structures of R163K in two different crystal forms, with six and two subunits per asymmetric part of the unit cells, have been determined. All subunits of this mutant are in the active conformation while wt hTS crystallizes as the inactive conformer in similar mother liquors. The structures show differences in the environment of catalytic Cys195, which correlate with Cys195 thiol reactivity, as judged by its oxidation state. Calculations show that the molecular electrostatic potential at Cys195 differs between the subunits of the dimer. One of the dimers is asymmetric with a phosphate ion bound in only one of the subunits. In the absence of the phosphate ion, that is in the inhibitor-free enzyme, the tip of loop 47-53 is about 11 A away from the active site.

The R163K mutant of human thymidylate synthase is stabilized in an active conformation: structural asymmetry and reactivity of cysteine 195.,Gibson LM, Lovelace LL, Lebioda L Biochemistry. 2008 Apr 22;47(16):4636-43. Epub 2008 Mar 28. PMID:18370400<ref>PMID:18370400</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 2rda" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gibson LM]]
[[Category: Lebioda L]]
[[Category: Lovelace LL]]