3qdd | pdb_00003qdd

HSP90A N-terminal domain in complex with BIIB021

spinqualitylabelsall models 3qdd, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qdd is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 94M Gene: HSP90AA1, HSP90A, HSPC1, HSPCA (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [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. Publication Abstract from PubMed Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3 -d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90alpha binding assay (IC(50) = 1.1 vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells (EC(50) = 14 vs 38 nM). In a mouse model of gastric tumors (N87), 40 stops tumor growth at 5 mg/kg and causes partial tumor regressions at 10 mg/kg (po, qdx5). Under the same conditions, 14 stops tumor growth only at 120 mg/kg, and does not induce partial regressions. Thus, alkyne 40 is approximately 20-fold more efficacious than 14 in mice. EC144 Is a Potent Inhibitor of the Heat Shock Protein 90.,Shi J, Van de Water R, Hong K, Lamer RB, Weichert KW, Sandoval CM, Kasibhatla SR, Boehm MF, Chao J, Lundgren K, Timple N, Lough R, Ibanez G, Boykin C, Burrows FJ, Kehry MR, Yun TJ, Harning EK, Ambrose C, Thompson J, Bixler SA, Dunah A, Snodgrass-Belt P, Arndt J, Enyedy IJ, Li P, Hong VS, McKenzie A, Biamonte MA J Med Chem. 2012 Sep 13;55(17):7786-95. Epub 2012 Aug 31. PMID:22938030 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Protein structures

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