1jxq
From Proteopedia
(New page: 200px<br /> <applet load="1jxq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jxq, resolution 2.8Å" /> '''Structure of cleaved...) |
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| - | [[Image:1jxq.gif|left|200px]]<br /> | + | [[Image:1jxq.gif|left|200px]]<br /><applet load="1jxq" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1jxq" size=" | + | |
caption="1jxq, resolution 2.8Å" /> | caption="1jxq, resolution 2.8Å" /> | ||
'''Structure of cleaved, CARD domain deleted Caspase-9'''<br /> | '''Structure of cleaved, CARD domain deleted Caspase-9'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A critical step in the induction of apoptosis is the activation of the | + | A critical step in the induction of apoptosis is the activation of the apoptotic initiator caspase 9. We show that at its normal physiological concentration, caspase 9 is primarily an inactive monomer (zymogen), and that activity is associated with a dimeric species. At the high concentrations used for crystal formation, caspase 9 is dimeric, and the structure reveals two very different active-site conformations within each dimer. One site closely resembles the catalytically competent sites of other caspases, whereas in the second, expulsion of the "activation loop" disrupts the catalytic machinery. We propose that the inactive domain resembles monomeric caspase 9. Activation is induced by dimerization, with interactions at the dimer interface promoting reorientation of the activation loop. These observations support a model in which recruitment by Apaf-1 creates high local concentrations of caspase 9 to provide a pathway for dimer-induced activation. |
==About this Structure== | ==About this Structure== | ||
| - | 1JXQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PHQ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1JXQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PHQ:'>PHQ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JXQ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Liddington, R | + | [[Category: Liddington, R C.]] |
[[Category: Renatus, M.]] | [[Category: Renatus, M.]] | ||
| - | [[Category: Salvesen, G | + | [[Category: Salvesen, G S.]] |
| - | [[Category: Scott, F | + | [[Category: Scott, F L.]] |
| - | [[Category: Stennicke, H | + | [[Category: Stennicke, H R.]] |
[[Category: PHQ]] | [[Category: PHQ]] | ||
[[Category: protease-inhibitor complex]] | [[Category: protease-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:27:53 2008'' |
Revision as of 11:27, 21 February 2008
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Structure of cleaved, CARD domain deleted Caspase-9
Overview
A critical step in the induction of apoptosis is the activation of the apoptotic initiator caspase 9. We show that at its normal physiological concentration, caspase 9 is primarily an inactive monomer (zymogen), and that activity is associated with a dimeric species. At the high concentrations used for crystal formation, caspase 9 is dimeric, and the structure reveals two very different active-site conformations within each dimer. One site closely resembles the catalytically competent sites of other caspases, whereas in the second, expulsion of the "activation loop" disrupts the catalytic machinery. We propose that the inactive domain resembles monomeric caspase 9. Activation is induced by dimerization, with interactions at the dimer interface promoting reorientation of the activation loop. These observations support a model in which recruitment by Apaf-1 creates high local concentrations of caspase 9 to provide a pathway for dimer-induced activation.
About this Structure
1JXQ is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Dimer formation drives the activation of the cell death protease caspase 9., Renatus M, Stennicke HR, Scott FL, Liddington RC, Salvesen GS, Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14250-5. PMID:11734640
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