1tsd
From Proteopedia
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| - | [[ | + | ==THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89== |
| + | <StructureSection load='1tsd' size='340' side='right' caption='[[1tsd]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1tsd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TSD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TSD FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=F89:S)-2-(5(((1,2-DIHYDRO-3-METHYL-1-OXOBENZO(F)QUINAZOLIN-9-YL)METHYL)AMINO)1-OXO-2-ISOINDOLINYL)GLUTARIC+ACID'>F89</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene></td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tsd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1tsd RCSB], [http://www.ebi.ac.uk/pdbsum/1tsd PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == 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/ts/1tsd_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/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The anticancer drug 1843U89 inhibits thymidylate synthase (TS) at sub-nanomolar concentrations and is undergoing clinical trial. The 1.95 A crystal structure of Escherichia coli TS bound to the drug and dUMP reveals that the 1843U89 binding surface includes a hydrophobic patch that is normally buried. To reach this patch, 1843U89 inserts into the wall of the TS active site, resulting in a severe local distortion of the protein. In this new conformation, active-site groups that normally bind to the catalytic cofactor methylene-tetrahydrofolate instead bind to 1843U89 in new ways. This structure provides a rare example of a protein that can bind tightly to distinct substances using a single, flexible, binding surface. This has implications for drug design, as 1843U89 could not have been obtained from current structure-based approaches. | ||
| - | + | Ligand-induced distortion of an active site in thymidylate synthase upon binding anticancer drug 1843U89.,Weichsel A, Montfort WR Nat Struct Biol. 1995 Dec;2(12):1095-101. PMID:8846221<ref>PMID:8846221</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Thymidylate synthase|Thymidylate synthase]] | *[[Thymidylate synthase|Thymidylate synthase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Thymidylate synthase]] | [[Category: Thymidylate synthase]] | ||
Revision as of 23:47, 28 September 2014
THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89
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