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4cwt

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Revision as of 17:31, 5 August 2016

Human HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitor

Structural highlights

4cwt is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4cwf, 4cwn, 4cwo, 4cwp, 4cwq, 4cwr, 4cws
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. PMID:15937123 doi:10.1073/pnas.0407294102
↑ Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. PMID:11274138 doi:10.1074/jbc.C100055200
↑ 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. Fragment-based hit discovery and structure-based optimization of aminotriazoloquinazolines as novel Hsp90 inhibitors. Bioorg Med Chem. 2014 Jun 14. pii: S0968-0896(14)00415-5. doi:, 10.1016/j.bmc.2014.05.056. PMID:24980703 doi:http://dx.doi.org/10.1016/j.bmc.2014.05.056

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4cwt"

@@ Line 1: / Line 1: @@
 ==Human HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitor==
 <StructureSection load='4cwt' size='340' side='right' caption='[[4cwt]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cwf|4cwf]], [[4cwn|4cwn]], [[4cwo|4cwo]], [[4cwp|4cwp]], [[4cwq|4cwq]], [[4cwr|4cwr]], [[4cws|4cws]]</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=4cwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cwt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cwt RCSB], [http://www.ebi.ac.uk/pdbsum/4cwt 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=4cwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cwt OCA], [http://pdbe.org/4cwt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cwt RCSB], [http://www.ebi.ac.uk/pdbsum/4cwt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cwt ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, 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 Proteins|Heat Shock Proteins]]
 == References ==
 <references/>

4cwt

From Proteopedia

Revision as of 17:31, 5 August 2016

Human HSP90 alpha N-terminal domain in complex with an Aminotriazoloquinazoline inhibitor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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