3f81
From Proteopedia
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- | [[ | + | ==Interaction of VHR with SA3== |
+ | <StructureSection load='3f81' size='340' side='right' caption='[[3f81]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
+ | == Structural highlights == | ||
+ | <table><tr><td colspan='2'>[[3f81]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F81 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F81 FirstGlance]. <br> | ||
+ | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=STT:2-(5-METHYL-4-OXO-2-THIOXO-2,4-DIHYDRO-3H-1LAMBDA~4~,3-THIAZOL-3-YL)ETHANESULFONIC+ACID'>STT</scene></td></tr> | ||
+ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DUSP3, VHR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
+ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3f81 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f81 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f81 RCSB], [http://www.ebi.ac.uk/pdbsum/3f81 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/f8/3f81_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 == | ||
+ | Loss of VHR phosphatase causes cell cycle arrest in HeLa carcinoma cells, suggesting that VHR inhibition may be a useful approach to halt the growth of cancer cells. We recently reported that VHR is upregulated in several cervix cancer cell lines as well as in carcinomas of the uterine cervix. Here we report the development of multidentate small-molecule inhibitors of VHR that inhibit its enzymatic activity at nanomolar concentrations and exhibit antiproliferative effects on cervix cancer cells. Chemical library screening was used to identify hit compounds, which were further prioritized in profiling and kinetic experiments. SAR analysis was applied in the search for analogs with improved potency and selectivity, resulting in the discovery of novel inhibitors that are able to interact with both the phosphate-binding pocket and several distinct hydrophobic regions within VHR's active site. This multidentate binding mode was confirmed by X-ray crystallography. The inhibitors decreased the proliferation of cervix cancer cells, while growth of primary normal keratinocytes was not affected. These compounds may be a starting point to develop drugs for the treatment of cervical cancer. | ||
- | + | Multidentate small-molecule inhibitors of vaccinia H1-related (VHR) phosphatase decrease proliferation of cervix cancer cells.,Wu S, Vossius S, Rahmouni S, Miletic AV, Vang T, Vazquez-Rodriguez J, Cerignoli F, Arimura Y, Williams S, Hayes T, Moutschen M, Vasile S, Pellecchia M, Mustelin T, Tautz L J Med Chem. 2009 Nov 12;52(21):6716-23. PMID:19888758<ref>PMID:19888758</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
- | + | == References == | |
- | + | <references/> | |
- | + | __TOC__ | |
- | + | </StructureSection> | |
- | + | ||
- | == | + | |
- | < | + | |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
- | [[Category: Mutelin, T | + | [[Category: Mutelin, T]] |
- | [[Category: Tautz, L | + | [[Category: Tautz, L]] |
- | [[Category: Wu, S | + | [[Category: Wu, S]] |
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
[[Category: Inhibitor]] | [[Category: Inhibitor]] | ||
[[Category: Protein dual-specificity phosphatase]] | [[Category: Protein dual-specificity phosphatase]] | ||
[[Category: Protein phosphatase]] | [[Category: Protein phosphatase]] |
Revision as of 08:48, 26 November 2014
Interaction of VHR with SA3
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