6aol | pdb_00006aol

Structure of molecular chaperone Grp94 bound to selective inhibitor methyl 3-chloro-2-(2-{2-[(4-fluorophenyl)methyl]phenyl}ethyl)-4,6-dihydroxybenzoate

spinqualitylabelsall models 6aol, resolution 2.76Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6aol is a 1 chain structure with sequence from Canis lupus familiaris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.764Å Ligands: P33, VC1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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). 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Protein structures

Proteopedia Page Contributors and Editors (what is this?)

OCA