4cwt: Difference between revisions
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==Human HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitor== | |||
<StructureSection load='4cwt' size='340' side='right'caption='[[4cwt]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4cwt]] 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=4CWT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CWT 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]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IK9:2-{[(2Z)-5-(1,3-BENZODIOXOL-5-YLMETHYL)-8-FLUORO-2-IMINO-2,3-DIHYDRO[1,2,4]TRIAZOLO[1,5-C]QUINAZOLIN-10-YL]AMINO}ETHANOL'>IK9</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=4cwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cwt OCA], [https://pdbe.org/4cwt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cwt RCSB], [https://www.ebi.ac.uk/pdbsum/4cwt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cwt 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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In 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<ref>PMID:24980703</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4cwt" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Heat Shock Protein structures|Heat Shock Protein structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Amboldi N]] | |||
[[Category: Brasca G]] | |||
[[Category: Caronni D]] | |||
[[Category: Casale E]] | |||
[[Category: Casuscelli F]] | |||
[[Category: Colombo N]] | |||
[[Category: Dalvit C]] | |||
[[Category: Felder ER]] | |||
[[Category: Fogliatto G]] | |||
[[Category: Isacchi A]] | |||
[[Category: Mantegani S]] | |||
[[Category: Polucci P]] | |||
[[Category: Riceputi L]] | |||
[[Category: Sola F]] | |||
[[Category: Visco C]] | |||
[[Category: Zuccotto F]] | |||
Latest revision as of 14:15, 9 May 2024
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
FunctionHS90A_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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