5uc4: Difference between revisions
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==Hsp90b N-terminal domain with inhibitors== | ==Hsp90b N-terminal domain with inhibitors== | ||
<StructureSection load='5uc4' size='340' side='right' caption='[[5uc4]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='5uc4' size='340' side='right'caption='[[5uc4]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5uc4]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5uc4]] is a 4 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=5UC4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UC4 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=83S:5-Hydroxy-4-(isoindoline-2-carbonyl)-2-isopropylbenzaldehyde'>83S</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | </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=83S:5-Hydroxy-4-(isoindoline-2-carbonyl)-2-isopropylbenzaldehyde'>83S</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5uc4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uc4 OCA], [https://pdbe.org/5uc4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uc4 RCSB], [https://www.ebi.ac.uk/pdbsum/5uc4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uc4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/HS90B_HUMAN HS90B_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:16478993</ref> <ref>PMID:19696785</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5uc4" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5uc4" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Heat Shock Protein structures|Heat Shock Protein structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Balch | [[Category: Large Structures]] | ||
[[Category: Deng | [[Category: Balch M]] | ||
[[Category: Matts | [[Category: Deng J]] | ||
[[Category: Peng | [[Category: Matts R]] | ||
[[Category: Peng S]] | |||
Latest revision as of 16:24, 4 October 2023
Hsp90b N-terminal domain with inhibitorsHsp90b N-terminal domain with inhibitors
Structural highlights
FunctionHS90B_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 PubMedThe 90 kDa heat shock protein (Hsp90) is a molecular chaperone responsible for folding proteins that are directly associated with cancer progression. Consequently, inhibition of the Hsp90 protein folding machinery results in a combinatorial attack on numerous oncogenic pathways. Seventeen small-molecule inhibitors of Hsp90 have entered clinical trials, all of which bind the Hsp90 N-terminus and exhibit pan-inhibitory activity against all four Hsp90 isoforms. pan-Inhibition of Hsp90 appears to be detrimental as toxicities have been reported alongside induction of the pro-survival heat shock response. The development of Hsp90 isoform-selective inhibitors represents an alternative approach towards the treatment of cancer that may limit some of the detriments. Described herein is a structure-based approach to design isoform-selective inhibitors of Hsp90beta, which induces the degradation of select Hsp90 clients without concomitant induction of Hsp90 levels. Together, these initial studies support the development of Hsp90beta-selective inhibitors as a method to overcome the detriments associated with pan-inhibition. Structure-guided design of an Hsp90beta N-terminal isoform-selective inhibitor.,Khandelwal A, Kent CN, Balch M, Peng S, Mishra SJ, Deng J, Day VW, Liu W, Subramanian C, Cohen M, Holzbeierlein JM, Matts R, Blagg BSJ Nat Commun. 2018 Jan 30;9(1):425. doi: 10.1038/s41467-017-02013-1. PMID:29382832[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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