4cwf: Difference between revisions
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==Human HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitor== | ==Human HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitor== | ||
<StructureSection load='4cwf' size='340' side='right' caption='[[4cwf]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='4cwf' size='340' side='right' caption='[[4cwf]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H05:5-PROPYL[1,2,4]TRIAZOLO[1,5-C]QUINAZOLIN-2-AMINE'>H05</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H05:5-PROPYL[1,2,4]TRIAZOLO[1,5-C]QUINAZOLIN-2-AMINE'>H05</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cwn|4cwn]], [[4cwo|4cwo]], [[4cwp|4cwp]], [[4cwq|4cwq]], [[4cwr|4cwr]], [[4cws|4cws]], [[4cwt|4cwt]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cwn|4cwn]], [[4cwo|4cwo]], [[4cwp|4cwp]], [[4cwq|4cwq]], [[4cwr|4cwr]], [[4cws|4cws]], [[4cwt|4cwt]]</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=4cwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cwf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cwf RCSB], [http://www.ebi.ac.uk/pdbsum/4cwf PDBsum]</span></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=4cwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cwf OCA], [http://pdbe.org/4cwf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cwf RCSB], [http://www.ebi.ac.uk/pdbsum/4cwf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cwf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4cwf" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Heat Shock Proteins|Heat Shock Proteins]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 19:31, 5 August 2016
Human HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitorHuman HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitor
Structural highlights
Function[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.[1] [2] Publication Abstract from PubMedIn the last decade the heat shock protein 90 (Hsp90) has emerged as a major therapeutic target and many efforts have been dedicated to the discovery of Hsp90 inhibitors as new potent anticancer agents. Here we report the identification of a novel class of Hsp90 inhibitors by means of a biophysical FAXS-NMR based screening of a library of fragments. The use of X-ray structure information combined with modeling studies enabled the fragment evolution of the initial triazoloquinazoline hit to a class of compounds with nanomolar potency and drug-like properties suited for further lead optimization. Fragment-based hit discovery and structure-based optimization of aminotriazoloquinazolines as novel Hsp90 inhibitors.,Casale E, Amboldi N, Brasca MG, Caronni D, Colombo N, Dalvit C, Felder ER, Fogliatto G, Galvani A, Isacchi A, Polucci P, Riceputi L, Sola F, Visco C, Zuccotto F, Casuscelli F Bioorg Med Chem. 2014 Jun 14. pii: S0968-0896(14)00415-5. doi:, 10.1016/j.bmc.2014.05.056. PMID:24980703[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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