4fea

Crystal structure of CASPASE-7 in Complex with allosteric inhibitor

spinqualitylabelsall models 4fea, resolution 3.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4fea is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.79Å Ligands: 0TE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CASP7_HUMAN Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death. Publication Abstract from PubMed Caspase inhibition is a promising approach for treating multiple diseases. Using a reconstituted assay and high-throughput screening, we identified a group of nonpeptide caspase inhibitors. These inhibitors share common chemical scaffolds, suggesting the same mechanism of action. They can inhibit apoptosis in various cell types induced by multiple stimuli; they can also inhibit caspase-1-mediated interleukin generation in macrophages, indicating potential anti-inflammatory application. While these compounds inhibit all the tested caspases, kinetic analysis indicates they do not compete for the catalytic sites of the enzymes. The cocrystal structure of one of these compounds with caspase-7 reveals that it binds to the dimerization interface of the caspase, another common structural element shared by all active caspases. Consistently, biochemical analysis demonstrates that the compound abates caspase-8 dimerization. Based on these kinetic, biochemical, and structural analyses, we suggest that these compounds are allosteric caspase inhibitors that function through binding to the dimerization interface of caspases. A Class of Allosteric Caspase Inhibitors Identified by High-Throughput Screening.,Feldman T, Kabaleeswaran V, Jang SB, Antczak C, Djaballah H, Wu H, Jiang X Mol Cell. 2012 Jul 10. PMID:22795132 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Caspase 3D structures

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