1nw9
From Proteopedia
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, resolution 2.40Å | |||||||
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Ligands: | |||||||
Gene: | BIRC4 OR API3 OR IAP3 OR XIAP (Homo sapiens) | ||||||
Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
Coordinates: | save as pdb, mmCIF, xml |
STRUCTURE OF CASPASE-9 IN AN INHIBITORY COMPLEX WITH XIAP-BIR3
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.
About this Structure
1NW9 is a Protein complex structure of sequences from Homo sapiens. 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 Sun Mar 30 22:36:25 2008