5ar0: Difference between revisions
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==HSP72 with adenosine-derived inhibitor== | |||
<StructureSection load='5ar0' size='340' side='right'caption='[[5ar0]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ar0]] 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=5AR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AR0 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GB8:(2R,3R,4S,5R)-2-(6-AMINO-8-((QUINOLIN-7-YLMETHYL)AMINO)-9H-PURIN-9-YL)-5-(HYDROXYMETHYL)TETRAHYDROFURAN-3,4-DIOL'>GB8</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5ar0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ar0 OCA], [https://pdbe.org/5ar0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ar0 RCSB], [https://www.ebi.ac.uk/pdbsum/5ar0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ar0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HS71A_HUMAN HS71A_HUMAN] In cooperation with other chaperones, Hsp70s stabilize preexistent proteins against aggregation and mediate the folding of newly translated polypeptides in the cytosol as well as within organelles. These chaperones participate in all these processes through their ability to recognize nonnative conformations of other proteins. They bind extended peptide segments with a net hydrophobic character exposed by polypeptides during translation and membrane translocation, or following stress-induced damage. In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223).<ref>PMID:16537599</ref> <ref>PMID:22528486</ref> <ref>PMID:23973223</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner. | |||
Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70.,Cheeseman MD, Westwood IM, Barbeau O, Rowlands M, Dobson S, Jones AM, Jeganathan F, Burke R, Kadi N, Workman P, Collins I, van Montfort RL, Jones K J Med Chem. 2016 May 11. PMID:27119979<ref>PMID:27119979</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5ar0" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Heat Shock Protein structures|Heat Shock Protein structures]] | ||
[[Category: Collins | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Jones | [[Category: Homo sapiens]] | ||
[[Category: Rowlands | [[Category: Large Structures]] | ||
[[Category: | [[Category: Barbeau O]] | ||
[[Category: | [[Category: Burke R]] | ||
[[Category: Cheeseman MD]] | |||
[[Category: Collins I]] | |||
[[Category: Dobson SE]] | |||
[[Category: Jeganathan F]] | |||
[[Category: Jones AM]] | |||
[[Category: Jones K]] | |||
[[Category: Rowlands MG]] | |||
[[Category: Westwood IM]] | |||
[[Category: Workman P]] | |||
[[Category: Van Montfort RLM]] | |||
Latest revision as of 14:15, 10 January 2024
HSP72 with adenosine-derived inhibitorHSP72 with adenosine-derived inhibitor
Structural highlights
FunctionHS71A_HUMAN In cooperation with other chaperones, Hsp70s stabilize preexistent proteins against aggregation and mediate the folding of newly translated polypeptides in the cytosol as well as within organelles. These chaperones participate in all these processes through their ability to recognize nonnative conformations of other proteins. They bind extended peptide segments with a net hydrophobic character exposed by polypeptides during translation and membrane translocation, or following stress-induced damage. In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223).[1] [2] [3] Publication Abstract from PubMedHSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner. Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70.,Cheeseman MD, Westwood IM, Barbeau O, Rowlands M, Dobson S, Jones AM, Jeganathan F, Burke R, Kadi N, Workman P, Collins I, van Montfort RL, Jones K J Med Chem. 2016 May 11. PMID:27119979[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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