1hvy
From Proteopedia
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==Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation== | ==Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation== | ||
| - | <StructureSection load='1hvy' size='340' side='right' caption='[[1hvy]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='1hvy' size='340' side='right'caption='[[1hvy]], [[Resolution|resolution]] 1.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1hvy]] is a 4 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1hvy]] is a 4 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=1HVY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HVY 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]] 1.9Å</td></tr> |
| - | <tr id=' | + | <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=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <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=1hvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hvy OCA], [https://pdbe.org/1hvy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hvy RCSB], [https://www.ebi.ac.uk/pdbsum/1hvy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hvy ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</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> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</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=1hvy ConSurf]. | </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=1hvy ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Thymidylate synthase (TS) is a major target in the chemotherapy of colorectal cancer and some other neoplasms while raltitrexed (Tomudex, ZD1694) is an antifolate inhibitor of TS approved for clinical use in several European countries. The crystal structure of the complex between recombinant human TS, dUMP, and raltitrexed has been determined at 1.9 A resolution. In contrast to the situation observed in the analogous complex of the rat TS, the enzyme is in the closed conformation and a covalent bond between the catalytic Cys 195 and dUMP is present in both subunits. This mode of ligand binding is similar to that of the analogous complex of the Escherichia coli enzyme. The only major differences observed are a direct hydrogen bond between His 196 and the O4 atom of dUMP and repositioning of the side chain of Tyr 94 by about 2 A. The thiophene ring of the drug is disordered between two parallel positions. | ||
| - | + | ==See Also== | |
| - | + | *[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]] | |
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== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Berger | + | [[Category: Berger SH]] |
| - | [[Category: Dunlap | + | [[Category: Dunlap RB]] |
| - | [[Category: Koli | + | [[Category: Koli S]] |
| - | [[Category: Lebioda | + | [[Category: Lebioda L]] |
| - | [[Category: Minor | + | [[Category: Minor W]] |
| - | [[Category: Phan | + | [[Category: Phan J]] |
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Current revision
Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation
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Categories: Homo sapiens | Large Structures | Berger SH | Dunlap RB | Koli S | Lebioda L | Minor W | Phan J
