1nw9: Difference between revisions

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[[Image:1nw9.gif|left|200px]]
[[Image:1nw9.png|left|200px]]


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==Overview==
{{ABSTRACT_12620238}}
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.


==About this Structure==
==About this Structure==
1NW9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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].  
1NW9 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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==
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:[http://www.ncbi.nlm.nih.gov/pubmed/12620238 12620238]
[[Category: Caspases]]
[[Category: Caspases]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Dimerization]]
[[Category: Dimerization]]
[[Category: Xiap]]
[[Category: Xiap]]
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