3nkf | pdb_00003nkf

Crystal structure of human ligand-free mature caspase-6 with intersubunit linker attached

spinqualitylabelsall models 3nkf, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3nkf is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 3k7e, 2wdp Activity: Caspase-6, with EC number 3.4.22.59 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CASP6_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves poly(ADP-ribose) polymerase in vitro, as well as lamins. Overexpression promotes programmed cell death. Publication Abstract from PubMed Caspase-6 is an apoptotic cysteine protease that also governs disease progression in Huntington's and Alzheimer's diseases. Caspase-6 is of great interest as a target for treatment of these neurodegenerative diseases; however, the molecular basis of caspase-6 function and regulation remains poorly understood. In the recently reported structure of caspase-6, the 60's and 130's helices at the base of the substrate-binding groove extend upward, in a conformation entirely different from that of any other caspase. Presently, the central question about caspase-6 structure and function is whether the extended conformation is the catalytically competent conformation or whether the extended helices must undergo a large conformational rearrangement in order to bind substrate. We have generated a series of caspase-6 cleavage variants, including a novel constitutively two-chain form, and determined crystal structures of caspase-6 with and without the intersubunit linker. This series allows evaluation of the role of the prodomain and intersubunit linker on caspase-6 structure and function before and after substrate binding. Caspase-6 is inherently more stable than closely related caspases. Cleaved caspase-6 with both the prodomain and the linker present is the most stable, indicating that these two regions act in concert to increase stability, but maintain the extended conformation in the unliganded state. Moreover, these data suggest that caspase-6 undergoes a significant conformational change upon substrate binding, adopting a structure that is more like canonical caspases. Substrate-Induced Conformational Changes Occur in All Cleaved Forms of Caspase-6.,Vaidya S, Velazquez-Delgado EM, Abbruzzese G, Hardy JA J Mol Biol. 2010 Nov 25. PMID:21111746 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Caspase 3D structures

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