4l91 | pdb_00004l91

Crystal structure of Human Hsp90 with X29

spinqualitylabelsall models 4l91, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4l91 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: X29 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 Heat shock protein 90 (HSP90) is a molecular chaperone to fold and maintain the proper conformation of many signaling proteins, especially some oncogenic proteins and mutated unstable proteins. Inhibition of HSP90 was recognized as an effective approach to simultaneously suppress several aberrant signaling pathways, and therefore it was considered as a novel target for cancer therapy. Here, by integrating several techniques including the fragment-based drug discovery method, fragment merging, computer aided inhibitor optimization, and structure-based drug design, we were able to identify a series of HSP90 inhibitors. Among them, inhibitors 13, 32, 36 and 40 can inhibit HSP90 with IC50 about 20-40 nM, which is at least 200-fold more potent than initial fragments in the protein binding assay. These new HSP90 inhibitors not only explore interactions with an under-studied subpocket, also offer new chemotypes for the development of novel HSP90 inhibitors as anticancer drugs. Identification of a new series of potent diphenol HSP90 inhibitors by fragment merging and structure-based optimization.,Ren J, Li J, Wang Y, Chen W, Shen A, Liu H, Chen D, Cao D, Li Y, Zhang N, Xu Y, Geng M, He J, Xiong B, Shen J Bioorg Med Chem Lett. 2014 Jun 1;24(11):2525-9. doi: 10.1016/j.bmcl.2014.03.100. , Epub 2014 Apr 8. PMID:24751441 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