4hqr

Crystal Structure of mutant form of Caspase-7

spinqualitylabelsall models 4hqr, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hqr is a 4 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 3Å Ligands: ACE, ASJ 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-7 is expressed as a proenzyme and is activated by initiator caspases upon the transmission of cell-death signals. Despite extensive structural and biochemical analyses, many questions regarding the mechanism of caspase-7 activation remain unanswered. Caspase-7 is auto-activated during overexpression in Escherichia coli, even in the absence of initiator caspases, indicating that procaspase-7 has intrinsic catalytic activity. When variants of procaspase-7 with altered L2 loops were prepared, a variant with six inserted amino acids showed meaningful catalytic activity which was inhibited by Ac-DEVD-CHO. The kinetic constants of the procaspase-7 variant were determined and its three-dimensional structure was solved with and without bound inhibitor. The homodimeric procaspase-7 bound to the inhibitor revealed an asymmetry. One monomer formed a complete active site bound to the inhibitor in collaboration with the L2 loop from the other monomer, whereas the other monomer had an incomplete active site despite the bound inhibitor. Consequently, the two L2 loops in homodimeric procaspase-7 served as inherent L2 and L2' loops forming one complete active site. These data represent the first three-dimensional structure of a procaspase-7 variant bound to a specific inhibitor, Ac-DEVD-CHO, and provide insight into the folding mechanism during caspase-7 activation and the basal activity level of procaspase-7. Structural asymmetry of procaspase-7 bound to a specific inhibitor.,Kang HJ, Lee YM, Bae KH, Kim SJ, Chung SJ Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1514-21. doi:, 10.1107/S0907444913010196. Epub 2013 Jul 18. PMID:23897474 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Caspase 3D structures

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