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5ttz
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Grp94 bound to isoform-selective inhibitor methyl 2-(2-(1-(4-bromobenzyl)-1H-imidazol-2-yl)ethyl)-3-chloro-4,6-dihydroxybenzoate== | |
| + | <StructureSection load='5ttz' size='340' side='right' caption='[[5ttz]], [[Resolution|resolution]] 2.71Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5ttz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TTZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TTZ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7KY:methyl+2-(2-{1-[(4-bromophenyl)methyl]-1H-imidazol-2-yl}ethyl)-3-chloro-4,6-dihydroxybenzoate'>7KY</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></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=5ttz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ttz OCA], [http://pdbe.org/5ttz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ttz RCSB], [http://www.ebi.ac.uk/pdbsum/5ttz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ttz ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ENPL_CANLF ENPL_CANLF]] Molecular chaperone that functions in the processing and transport of secreted proteins. When associated with CNPY3, required for proper folding of Toll-like receptors. Functions in endoplasmic reticulum associated degradation (ERAD). Has ATPase activity (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The heat shock protein 90 (Hsp90) family of molecular chaperones regulates protein homeostasis, folding, and degradation. The ER-resident Hsp90 isoform, glucose-regulated protein 94 (Grp94), promotes the aggregation of mutant forms of myocilin, a protein associated with primary open-angle glaucoma. While inhibition of Grp94 promotes the degradation of mutant myocilin in vitro, to date no Grp94-selective inhibitors have been investigated in vivo. Here, a Grp94-selective inhibitor facilitated mutant myocilin degradation and rescued phenotypes in a transgenic mouse model of hereditary primary open-angle glaucoma. Ocular toxicities previously associated with pan-Hsp90 inhibitors were not evident with our Grp94-selective inhibitor, 4-Br-BnIm. Our study suggests that selective inhibition of a distinct Hsp90 family member holds translational promise for ocular and other diseases associated with cell stress and protein misfolding. | ||
| - | + | Isoform-selective Hsp90 inhibition rescues model of hereditary open-angle glaucoma.,Stothert AR, Suntharalingam A, Tang X, Crowley VM, Mishra SJ, Webster JM, Nordhues BA, Huard DJE, Passaglia CL, Lieberman RL, Blagg BSJ, Blair LJ, Koren J 3rd, Dickey CA Sci Rep. 2017 Dec 20;7(1):17951. doi: 10.1038/s41598-017-18344-4. PMID:29263415<ref>PMID:29263415</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5ttz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Huard, D J.E]] | ||
| + | [[Category: Lieberman, R L]] | ||
| + | [[Category: Atp binding site]] | ||
| + | [[Category: Bnim scaffold]] | ||
| + | [[Category: Chaperone - inhibitor complex]] | ||
Revision as of 08:25, 10 January 2018
Crystal structure of Grp94 bound to isoform-selective inhibitor methyl 2-(2-(1-(4-bromobenzyl)-1H-imidazol-2-yl)ethyl)-3-chloro-4,6-dihydroxybenzoate
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