View source for 1tda


==STRUCTURES OF THYMIDYLATE SYNTHASE WITH A C-TERMINAL DELETION: ROLE OF THE C-TERMINUS IN ALIGNMENT OF D/UMP AND CH2H4FOLATE==
<StructureSection load='1tda' size='340' side='right'caption='[[1tda]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1tda]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TDA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </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=1tda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tda OCA], [https://pdbe.org/1tda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tda RCSB], [https://www.ebi.ac.uk/pdbsum/1tda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tda ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/TYSY_LACCA TYSY_LACCA]] Provides the sole de novo source of dTMP for DNA biosynthesis. 
== 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/td/1tda_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=1tda ConSurf].
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== Publication Abstract from PubMed ==
Thymidylate synthase undergoes a major conformational change upon ligand binding, where the carboxyl terminus displays the largest movement (approximately 4 A). This movement from an "open" unliganded state to the "closed" complexed conformation plays a crucial role in the correct orientation of substrates and in product formation. The mutant lacking the C-terminal valine (V316Am) of the enzyme is inactive. X-ray crystal structures of V316Am and its complexes with dUMP, FdUMP, and both FdUMP and CH2H4folate are described. The structures show that ligands are bound within the active site, but in different modes than those in analogous, wild-type thymidylate synthase structures. The 2.7-A binary complex structures of V316Am with FdUMP and dUMP show that the pyrimidine and ribose moieties of the nucleotides are pivoted approximately 20 degrees around the 3'-hydroxyl compared to dUMP in the wild-type enzyme. The 2.7-A crystal structure of V316Am complexed with cofactor, CH2H4folate, and the substrate analog, FdUMP, shows these ligands bound in an open conformation similar to that of the unliganded enzyme. In this ternary complex, the imidazolidine ring of the cofactor is open and has reacted with water to form 5-HOCH2H4folate. 5-HOCH2H4folate is structural evidence for the 5-iminium ion intermediate, which is the proposed reactive form of CH2H4folate. The altered ligand binding modes observed in the three V316Am complex structures open new venues for the design of novel TS inhibitors.

Structures of thymidylate synthase with a C-terminal deletion: role of the C-terminus in alignment of 2'-deoxyuridine 5'-monophosphate and 5,10-methylenetetrahydrofolate.,Perry KM, Carreras CW, Chang LC, Santi DV, Stroud RM Biochemistry. 1993 Jul 20;32(28):7116-25. PMID:8343503<ref>PMID:8343503</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus a von freudenreich 1890]]
[[Category: Large Structures]]
[[Category: Thymidylate synthase]]
[[Category: Carreras, C W]]
[[Category: Chang, L C]]
[[Category: Perry, K M]]
[[Category: Santi, D V]]
[[Category: Stroud, R M]]