View source for 6aom


==Structure of molecular chaperone Grp94 bound to selective inhibitor methyl 2-[2-(2-benzylphenyl)ethyl]-3-chloro-4,6-dihydroxybenzoate==
<StructureSection load='6aom' size='340' side='right'caption='[[6aom]], [[Resolution|resolution]] 2.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6aom]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AOM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AOM 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]] 2.87&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=VC5:methyl+2-[2-(2-benzylphenyl)ethyl]-3-chloro-4,6-dihydroxybenzoate'>VC5</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=6aom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aom OCA], [https://pdbe.org/6aom PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aom RCSB], [https://www.ebi.ac.uk/pdbsum/6aom PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aom ProSAT]</span></td></tr>
</table>
== Function ==
[https://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 ==
Glucose regulated protein 94 (Grp94) is the endoplasmic reticulum (ER) resident isoform of the 90 kDa heat shock protein (Hsp90) family and its inhibition represents a promising therapeutic target for the treatment of many diseases. Modification of the first generation cis-amide bioisostere imidazole to alter the angle between the resorcinol ring and the benzyl side chain via cis-amide replacements produced compounds with improved Grp94 affinity and selectivity. Structure-activity relationship studies led to the discovery of compound 30, which exhibits 540 nm affinity and 73-fold selectivity towards Grp94. Grp94 is responsible for the maturation and trafficking of proteins associated with cell signaling and motility, including select integrins. The Grp94-selective inhibitor 30 was shown to exhibit potent anti-migratory effects against multiple aggressive and metastatic cancers.

Second Generation Grp94-Selective Inhibitors Provide Opportunities for the Inhibition of Metastatic Cancer.,Crowley VM, Huard DJE, Lieberman RL, Blagg BSJ Chemistry. 2017 Aug 30. doi: 10.1002/chem.201703398. PMID:28857290<ref>PMID:28857290</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6aom" style="background-color:#fffaf0;"></div>

==See Also==
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Canis lupus familiaris]]
[[Category: Large Structures]]
[[Category: Huard DJE]]
[[Category: Lieberman RL]]