1pyo
|
Crystal Structure of Human Caspase-2 in Complex with Acetyl-Leu-Asp-Glu-Ser-Asp-cho
OverviewOverview
The cell death protease caspase-2 has recently been recognized as the most, apical caspase in the apoptotic cascade ignited during cell stress, signaling. Cytotoxic stress, such as that caused by cancer therapies, leads to activation of caspase-2, which acts as a direct effector of the, mitochondrion-dependent apoptotic pathway resulting in programmed cell, death. Here we report the x-ray structure of caspase-2 in complex with the, inhibitor acetyl-Leu-Asp-Glu-Ser-Asp-aldehyde at 1.65-A resolution., Compared with other caspases, significant structural differences prevail, in the active site region and the dimer interface. The structure reveals, the hydrophobic properties of the S5 specificity pocket, which is unique, to caspase-2, and provides the details of the inhibitor-protein, interactions in subsites S1-S4. These features form the basis of caspase-2, specificity and allow the design of caspase-2-directed ligands for medical, and analytical use. Another unique feature of caspase-2 is a disulfide, bridge at the dimer interface, which covalently links the two monomers., Consistent with this finding, caspase-2 exists as a (p19/p12)2 dimer in, solution, even in the absence of substrates or inhibitors. The, intersubunit disulfide bridge stabilizes the dimeric form of caspase-2, whereas all other long prodomain caspases exist as monomers in solution, and dimer formation is driven by ligand binding. Therefore, the central, disulfide bridge appears to represent a novel way of dimer stabilization, in caspases.
About this StructureAbout this Structure
1PYO is a Protein complex structure of sequences from Homo sapiens with ACE as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of caspase-2, apical initiator of the intrinsic apoptotic pathway., Schweizer A, Briand C, Grutter MG, J Biol Chem. 2003 Oct 24;278(43):42441-7. Epub 2003 Aug 14. PMID:12920126
Page seeded by OCA on Mon Nov 12 18:48:45 2007