4nh9: Difference between revisions
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==Correlation between chemotype-dependent binding conformations of HSP90 alpha/beta and isoform selectivity== | |||
<StructureSection load='4nh9' size='340' side='right' caption='[[4nh9]], [[Resolution|resolution]] 2.77Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4nh9]] 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=4NH9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NH9 FirstGlance]. <br> | |||
</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]], [[4nh8|4nh8]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90B1, GRP94, TRA1 ([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=4nh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nh9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nh9 RCSB], [http://www.ebi.ac.uk/pdbsum/4nh9 PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/ENPL_HUMAN ENPL_HUMAN]] Molecular chaperone that functions in the processing and transport of secreted proteins. When associated with CNPY3, required for proper folding of Toll-like receptors (By similarity). Functions in endoplasmic reticulum associated degradation (ERAD). Has ATPase activity.<ref>PMID:18264092</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> | |||
== | ==See Also== | ||
*[[Endoplasmin|Endoplasmin]] | |||
[[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 structure]] | [[Category: A/b structure]] | ||
[[Category: Chaperone]] | [[Category: Chaperone]] | ||
[[Category: Endoplasmic reticulum]] | [[Category: Endoplasmic reticulum]] | ||
