View source for 4fgt


==Allosteric peptidic inhibitor of human thymidylate synthase that stabilizes inactive conformation of the enzyme.==
<StructureSection load='4fgt' size='340' side='right'caption='[[4fgt]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4fgt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FGT 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4fgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fgt OCA], [https://pdbe.org/4fgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fgt RCSB], [https://www.ebi.ac.uk/pdbsum/4fgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fgt 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Allosteric peptide inhibitors of thymidylate synthase (hTS) bind to the dimer interface and stabilize the inactive form of the protein. Four interface residues were mutated to alanine, and interaction studies were employed to decode the key role of these residues in the peptide molecular recognition. This led to the identification of three crucial interface residues F59, L198, and Y202 that impart activity to the peptide inhibitors and suggest the binding area for further inhibitor design.

Alanine mutants of the interface residues of human thymidylate synthase decode key features of the binding mode of allosteric anticancer peptides.,Tochowicz A, Santucci M, Saxena P, Guaitoli G, Trande M, Finer-Moore J, Stroud RM, Costi MP J Med Chem. 2015 Jan 22;58(2):1012-8. doi: 10.1021/jm5011176. Epub 2014 Dec 29. PMID:25427005<ref>PMID:25427005</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4fgt" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Costi MP]]
[[Category: Finer-Moore J]]
[[Category: Stroud RM]]
[[Category: Tochowicz A]]