1nw9
From Proteopedia
(New page: 200px<br /> <applet load="1nw9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nw9, resolution 2.40Å" /> '''STRUCTURE OF CASPAS...) |
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| - | [[Image:1nw9.gif|left|200px]]<br /> | + | [[Image:1nw9.gif|left|200px]]<br /><applet load="1nw9" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1nw9" size=" | + | |
caption="1nw9, resolution 2.40Å" /> | caption="1nw9, resolution 2.40Å" /> | ||
'''STRUCTURE OF CASPASE-9 IN AN INHIBITORY COMPLEX WITH XIAP-BIR3'''<br /> | '''STRUCTURE OF CASPASE-9 IN AN INHIBITORY COMPLEX WITH XIAP-BIR3'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The inhibitor of apoptosis (IAP) proteins potently inhibit the catalytic | + | The inhibitor of apoptosis (IAP) proteins potently inhibit the catalytic activity of caspases. While profound insight into the inhibition of the effector caspases has been gained in recent years, the mechanism of how the initiator caspase-9 is regulated by IAPs remains enigmatic. This paper reports the crystal structure of caspase-9 in an inhibitory complex with the third baculoviral IAP repeat (BIR3) of XIAP at 2.4 A resolution. The structure reveals that the BIR3 domain forms a heterodimer with a caspase-9 monomer. Strikingly, the surface of caspase-9 that interacts with BIR3 also mediates its homodimerization. We demonstrate that monomeric caspase-9 is catalytically inactive due to the absence of a supporting sequence element that could be provided by homodimerization. Thus, XIAP sequesters caspase-9 in a monomeric state, which serves to prevent catalytic activity. These studies, in conjunction with other observations, define a unified mechanism for the activation of all caspases. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1NW9 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 ZN as [http://en.wikipedia.org/wiki/ligand ligand]. The following page contains interesting information on the relation of 1NW9 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb56_1.html Caspases]]. Full crystallographic information is available from [http:// | + | 1NW9 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=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. The following page contains interesting information on the relation of 1NW9 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb56_1.html Caspases]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NW9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Alnemri, E | + | [[Category: Alnemri, E S.]] |
[[Category: Chai, J.]] | [[Category: Chai, J.]] | ||
[[Category: Fairman, R.]] | [[Category: Fairman, R.]] | ||
[[Category: Li, P.]] | [[Category: Li, P.]] | ||
| - | [[Category: Riedl, S | + | [[Category: Riedl, S J.]] |
| - | [[Category: Rigotti, D | + | [[Category: Rigotti, D J.]] |
[[Category: Shi, Y.]] | [[Category: Shi, Y.]] | ||
| - | [[Category: Shiozaki, E | + | [[Category: Shiozaki, E N.]] |
| - | [[Category: Srinivasula, S | + | [[Category: Srinivasula, S M.]] |
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: apoptosis]] | [[Category: apoptosis]] | ||
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[[Category: xiap]] | [[Category: xiap]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:10:46 2008'' |
Revision as of 12:10, 21 February 2008
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STRUCTURE OF CASPASE-9 IN AN INHIBITORY COMPLEX WITH XIAP-BIR3
Contents |
Overview
The inhibitor of apoptosis (IAP) proteins potently inhibit the catalytic activity of caspases. While profound insight into the inhibition of the effector caspases has been gained in recent years, the mechanism of how the initiator caspase-9 is regulated by IAPs remains enigmatic. This paper reports the crystal structure of caspase-9 in an inhibitory complex with the third baculoviral IAP repeat (BIR3) of XIAP at 2.4 A resolution. The structure reveals that the BIR3 domain forms a heterodimer with a caspase-9 monomer. Strikingly, the surface of caspase-9 that interacts with BIR3 also mediates its homodimerization. We demonstrate that monomeric caspase-9 is catalytically inactive due to the absence of a supporting sequence element that could be provided by homodimerization. Thus, XIAP sequesters caspase-9 in a monomeric state, which serves to prevent catalytic activity. These studies, in conjunction with other observations, define a unified mechanism for the activation of all caspases.
Disease
Known diseases associated with this structure: Lymphoproliferative syndrome, X-linked, 2 OMIM:[300079]
About this Structure
1NW9 is a Protein complex structure of sequences from Homo sapiens with as ligand. The following page contains interesting information on the relation of 1NW9 with [Caspases]. Full crystallographic information is available from OCA.
Reference
Mechanism of XIAP-mediated inhibition of caspase-9., Shiozaki EN, Chai J, Rigotti DJ, Riedl SJ, Li P, Srinivasula SM, Alnemri ES, Fairman R, Shi Y, Mol Cell. 2003 Feb;11(2):519-27. PMID:12620238
Page seeded by OCA on Thu Feb 21 14:10:46 2008
Categories: Caspases | Homo sapiens | Protein complex | Alnemri, E S. | Chai, J. | Fairman, R. | Li, P. | Riedl, S J. | Rigotti, D J. | Shi, Y. | Shiozaki, E N. | Srinivasula, S M. | ZN | Apoptosis | Caspase activation | Caspase inhibition | Caspase-9 | Dimerization | Xiap
