2xzd

Caspase-3 in Complex with an Inhibitory DARPin-3.4

spinqualitylabelsall models 2xzd, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xzd 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 2.1Å Ligands: CSO, MPD, MRD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CASP3_HUMAN Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. Publication Abstract from PubMed Dysregulation of apoptosis is associated with several human diseases. The main apoptotic mediators are caspases, which propagate death signals to downstream targets. Executioner caspase-3 is responsible for the majority of cleavage events and its therapeutic potential is of high interest with to date several available active site peptide inhibitors. These molecules inhibit caspase-3, but also homologous caspases. Here, we describe caspase-3 specific inhibitors D3.4 and D3.8, which have been selected from a library of designed ankyrin repeat proteins (DARPins). The crystal structures of D3.4 and mutants thereof show how high specificity and inhibition is achieved. They also show similarities in the binding mode with that of the natural caspase inhibitor XIAP (X-linked inhibitor of apoptosis). The kinetic data reveal a competitive inhibition mechanism. D3.4 is specific for caspase-3 and does not bind the highly homologous caspase-7. D3.4 therefore is an excellent tool to define the precise role of caspase-3 in the various apoptotic pathways. Specific Inhibition of Caspase-3 by a Competitive DARPin: Molecular Mimicry between Native and Designed Inhibitors.,Schroeder T, Barandun J, Flutsch A, Briand C, Mittl PR, Grutter MG Structure. 2013 Jan 15. pii: S0969-2126(12)00466-2. doi:, 10.1016/j.str.2012.12.011. PMID:23333429 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Caspase 3D structures

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