3n5e: Difference between revisions
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<StructureSection load='3n5e' size='340' side='right'caption='[[3n5e]], [[Resolution|resolution]] 2.26Å' scene=''> | <StructureSection load='3n5e' size='340' side='right'caption='[[3n5e]], [[Resolution|resolution]] 2.26Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3n5e]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3n5e]] is a 3 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=3N5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N5E FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.26Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SCH:S-METHYL-THIO-CYSTEINE'>SCH</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=3n5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5e OCA], [https://pdbe.org/3n5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n5e RCSB], [https://www.ebi.ac.uk/pdbsum/3n5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n5e ProSAT]</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=3n5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n5e OCA], [https://pdbe.org/3n5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n5e RCSB], [https://www.ebi.ac.uk/pdbsum/3n5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n5e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cardinale D]] | |||
[[Category: Cardinale | [[Category: Costi MP]] | ||
[[Category: Costi | [[Category: Ferrari S]] | ||
[[Category: Ferrari | [[Category: Guaitoli G]] | ||
[[Category: Guaitoli | [[Category: Luciani R]] | ||
[[Category: Luciani | [[Category: Mangani S]] | ||
[[Category: Mangani | [[Category: Myllykallio H]] | ||
[[Category: Myllykallio | [[Category: Pozzi C]] | ||
[[Category: Pozzi | [[Category: Tondi D]] | ||
[[Category: Tondi | |||
Latest revision as of 12:09, 6 September 2023
Crystal Structure of human thymidylate synthase bound to a peptide inhibitorCrystal Structure of human thymidylate synthase bound to a peptide inhibitor
Structural highlights
FunctionTYSY_HUMAN Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.[1] Publication Abstract from PubMedHuman thymidylate synthase is a homodimeric enzyme that plays a key role in DNA synthesis and is a target for several clinically important anticancer drugs that bind to its active site. We have designed peptides to specifically target its dimer interface. Here we show through X-ray diffraction, spectroscopic, kinetic, and calorimetric evidence that the peptides do indeed bind at the interface of the dimeric protein and stabilize its di-inactive form. The "LR" peptide binds at a previously unknown binding site and shows a previously undescribed mechanism for the allosteric inhibition of a homodimeric enzyme. It inhibits the intracellular enzyme in ovarian cancer cells and reduces cellular growth at low micromolar concentrations in both cisplatin-sensitive and -resistant cells without causing protein overexpression. This peptide demonstrates the potential of allosteric inhibition of hTS for overcoming platinum drug resistance in ovarian cancer. Protein-protein interface-binding peptides inhibit the cancer therapy target human thymidylate synthase.,Cardinale D, Guaitoli G, Tondi D, Luciani R, Henrich S, Salo-Ahen OM, Ferrari S, Marverti G, Guerrieri D, Ligabue A, Frassineti C, Pozzi C, Mangani S, Fessas D, Guerrini R, Ponterini G, Wade RC, Costi MP Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):E542-9. doi:, 10.1073/pnas.1104829108. Epub 2011 Jul 27. PMID:21795601[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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