From Proteopedia
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| - | [[Image:1pyo.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1pyo.png|left|200px]] |
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| | {{STRUCTURE_1pyo| PDB=1pyo | SCENE= }} | | {{STRUCTURE_1pyo| PDB=1pyo | SCENE= }} |
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| - | '''Crystal Structure of Human Caspase-2 in Complex with Acetyl-Leu-Asp-Glu-Ser-Asp-cho'''
| + | ===Crystal Structure of Human Caspase-2 in Complex with Acetyl-Leu-Asp-Glu-Ser-Asp-cho=== |
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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_12920126}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12920126 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_12920126}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Caspase]] | | [[Category: Caspase]] |
| | [[Category: Thiol protease]] | | [[Category: Thiol protease]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:39:06 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:54:44 2008'' |
Revision as of 13:54, 27 July 2008
Template:STRUCTURE 1pyo
Crystal Structure of Human Caspase-2 in Complex with Acetyl-Leu-Asp-Glu-Ser-Asp-cho
Template:ABSTRACT PUBMED 12920126
About this Structure
1PYO is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Sun Jul 27 16:54:44 2008
