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4nh8
From Proteopedia
(Difference between revisions)
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| - | + | ==Correlation between chemotype-dependent binding conformations of HSP90 alpha/beta and isoform selectivity== | |
| - | + | <StructureSection load='4nh8' size='340' side='right' caption='[[4nh8]], [[Resolution|resolution]] 1.65Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[4nh8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NH8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NH8 FirstGlance]. <br> | |
| - | ==Function== | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2LC:2-FLUORO-6-[(3S)-TETRAHYDROFURAN-3-YLAMINO]-4-(3,6,6-TRIMETHYL-4-OXO-4,5,6,7-TETRAHYDRO-1H-INDOL-1-YL)BENZAMIDE'>2LC</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nh7|4nh7]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4nh8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nh8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nh8 RCSB], [http://www.ebi.ac.uk/pdbsum/4nh8 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
[[http://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> | [[http://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 == | ||
| + | HSP90 continues to be a target of interest for neurodegeneration indications. Selective knockdown of the HSP90 cytosolic isoforms alpha and beta is sufficient to reduce mutant huntingtin protein levels in vitro. Chemotype-dependent binding conformations of HSP90alpha/beta appear to strongly influence isoform selectivity. The rational design of HSP90alpha/beta inhibitors selective versus the mitochondrial (TRAP1) and endoplasmic reticulum (GRP94) isoforms offers a potential mitigating strategy for mechanism-based toxicities. Better tolerated HSP90 inhibitors would be attractive for targeting chronic neurodegenerative diseases such as Huntington's disease. | ||
| - | + | Correlation between chemotype-dependent binding conformations of HSP90alpha/beta and isoform selectivity-Implications for the structure-based design of HSP90alpha/beta selective inhibitors for treating neurodegenerative diseases.,Ernst JT, Liu M, Zuccola H, Neubert T, Beaumont K, Turnbull A, Kallel A, Vought B, Stamos D Bioorg Med Chem Lett. 2014 Jan 1;24(1):204-8. doi: 10.1016/j.bmcl.2013.11.036., Epub 2013 Nov 23. PMID:24332488<ref>PMID:24332488</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| - | [[Category: Ernst, J T | + | == References == |
| - | [[Category: Zuccola, H J | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Ernst, J T]] | ||
| + | [[Category: Zuccola, H J]] | ||
[[Category: A/b protein]] | [[Category: A/b protein]] | ||
[[Category: Chaperone]] | [[Category: Chaperone]] | ||
Revision as of 14:19, 25 December 2014
Correlation between chemotype-dependent binding conformations of HSP90 alpha/beta and isoform selectivity
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