4ehr | pdb_00004ehr

Crystal structure of Bcl-Xl complex with 4-(5-butyl-3-(hydroxymethyl)-1-phenyl-1h-pyrazol-4-yl)-3-(3,4-dihydro-2(1h)-isoquinolinylcarbonyl)-n-((2-(trimethylsilyl)ethyl)sulfonyl)benzamide

spinqualitylabelsall models 4ehr, resolution 2.09Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ehr 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: 0Q5, IMD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis. Isoform Bcl-X(S) promotes apoptosis. Publication Abstract from PubMed 5-Butyl-1,4-diphenyl pyrazole and 2-amino-5-chloro pyrimidine acylsulfonamides were developed as potent dual antagonists of Bcl-2 and Bcl-xL. Compounds were optimized for binding to the I88, L92, I95, and F99 pockets normally occupied by pro-apoptotic protein Bim. An X-ray crystal structure confirmed the proposed binding mode. Observation of cytochrome c release from isolated mitochondria in MV-411 cells provides further evidence of target inhibition. Compounds demonstrated submicromolar antiproliferative activity in Bcl-2/Bcl-xL dependent cell lines. Pyrazole and pyrimidine phenylacylsulfonamides as dual Bcl-2/Bcl-xL antagonists.,Schroeder GM, Wei D, Banfi P, Cai ZW, Lippy J, Menichincheri M, Modugno M, Naglich J, Penhallow B, Perez HL, Sack J, Schmidt RJ, Tebben A, Yan C, Zhang L, Galvani A, Lombardo LJ, Borzilleri RM Bioorg Med Chem Lett. 2012 Jun 15;22(12):3951-6. Epub 2012 Apr 30. PMID:22608393 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also B-cell lymphoma proteins 3D structures

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