5ic6

Crystal structure of caspase-7 DEVE peptide complex

spinqualitylabelsall models 5ic6, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ic6 is a 6 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: MKE 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 Caspases are a family of proteases found in all metazoans, including a dozen in humans, that drive the terminal stages of apoptosis as well as other cellular remodeling and inflammatory events. Caspases are named because they are cysteine class enzymes shown to cleave after aspartate residues. In the past decade, we and others have developed unbiased proteomic methods that collectively identified ~2000 native proteins cleaved during apoptosis after the signature aspartate residues. Here, we explore non-aspartate cleavage events and identify 100s of substrates cleaved after glutamate in both human and murine apoptotic samples. The extended consensus sequence patterns are virtually identical for the aspartate and glutamate cleavage sites suggesting they are cleaved by the same caspases. Detailed kinetic analyses of the dominant apoptotic executioner caspases-3 and -7 show that synthetic substrates containing DEVD downward arrow are cleaved only twofold faster than DEVE downward arrow, which is well within the 500-fold range of rates that natural proteins are cut. X-ray crystallography studies confirm that the two acidic substrates bind in virtually the same way to either caspases-3 or -7 with minimal adjustments to accommodate the larger glutamate. Lastly, during apoptosis we found 121 proteins cleaved after serine residues that have been previously annotated to be phosphorylation sites. We found that caspase-3, but not caspase-7, can cleave peptides containing DEVpS downward arrow at only threefold slower rate than DEVD downward arrow, but does not cleave the unphosphorylated serine peptide. There are only a handful of previously reported examples of proteins cleaved after glutamate and none after phosphorserine. Our studies reveal a much greater promiscuity for cleaving after acidic residues and the name 'cacidase' could aptly reflect this broader specificity.Cell Death and Differentiation advance online publication, 1 July 2016; doi:10.1038/cdd.2016.62. Cacidases: caspases can cleave after aspartate, glutamate and phosphoserine residues.,Seaman JE, Julien O, Lee PS, Rettenmaier TJ, Thomsen ND, Wells JA Cell Death Differ. 2016 Jul 1. doi: 10.1038/cdd.2016.62. PMID:27367566 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Caspase 3D structures

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