1pyo

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[[Image:1pyo.gif|left|200px]]<br /><applet load="1pyo" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1pyo.gif|left|200px]]
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caption="1pyo, resolution 1.65&Aring;" />
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'''Crystal Structure of Human Caspase-2 in Complex with Acetyl-Leu-Asp-Glu-Ser-Asp-cho'''<br />
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{{Structure
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|PDB= 1pyo |SIZE=350|CAPTION= <scene name='initialview01'>1pyo</scene>, resolution 1.65&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ACE:ACETYL GROUP'>ACE</scene>
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|ACTIVITY=
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|GENE= CASP2 OR ICH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Crystal Structure of Human Caspase-2 in Complex with Acetyl-Leu-Asp-Glu-Ser-Asp-cho'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1PYO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ACE:'>ACE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PYO OCA].
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1PYO is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PYO OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12920126 12920126]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12920126 12920126]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: thiol protease]]
[[Category: thiol protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:34:01 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:30:41 2008''

Revision as of 11:30, 20 March 2008


PDB ID 1pyo

Drag the structure with the mouse to rotate
, resolution 1.65Å
Ligands:
Gene: CASP2 OR ICH1 (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



Crystal Structure of Human Caspase-2 in Complex with Acetyl-Leu-Asp-Glu-Ser-Asp-cho


Overview

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 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

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