2bsm
From Proteopedia
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| - | [[Image:2bsm.gif|left|200px]]<br /><applet load="2bsm" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2bsm, resolution 2.05Å" /> | ||
| - | '''NOVEL, POTENT SMALL MOLECULE INHIBITORS OF THE MOLECULAR CHAPERONE HSP90 DISCOVERED THROUGH STRUCTURE-BASED DESIGN'''<br /> | ||
| - | == | + | ==Novel, potent small molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design== |
| + | <StructureSection load='2bsm' size='340' side='right'caption='[[2bsm]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2bsm]] is a 1 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=2BSM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BSM 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]] 2.05Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BSM:5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-(4-METHOXYPHENYL)-1H-PYRAZOLE-3-CARBOXAMIDE'>BSM</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=2bsm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bsm OCA], [https://pdbe.org/2bsm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bsm RCSB], [https://www.ebi.ac.uk/pdbsum/2bsm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bsm ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref> | ||
| + | == 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/bs/2bsm_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/main_output.php?pdb_ID=2bsm ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmacodynamic changes. Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG. | The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmacodynamic changes. Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG. | ||
| - | + | Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design.,Dymock BW, Barril X, Brough PA, Cansfield JE, Massey A, McDonald E, Hubbard RE, Surgenor A, Roughley SD, Webb P, Workman P, Wright L, Drysdale MJ J Med Chem. 2005 Jun 30;48(13):4212-5. PMID:15974572<ref>PMID:15974572</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2bsm" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Barril X]] | ||
| + | [[Category: Brough PA]] | ||
| + | [[Category: Cansfield JE]] | ||
| + | [[Category: Drysdale MJ]] | ||
| + | [[Category: Dymock BW]] | ||
| + | [[Category: Hubbard RE]] | ||
| + | [[Category: Massey A]] | ||
| + | [[Category: McDonald E]] | ||
| + | [[Category: Roughley SD]] | ||
| + | [[Category: Surgenor A]] | ||
| + | [[Category: Webb P]] | ||
| + | [[Category: Workman P]] | ||
| + | [[Category: Wright L]] | ||
Current revision
Novel, potent small molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design
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Categories: Homo sapiens | Large Structures | Barril X | Brough PA | Cansfield JE | Drysdale MJ | Dymock BW | Hubbard RE | Massey A | McDonald E | Roughley SD | Surgenor A | Webb P | Workman P | Wright L
