1nw9

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spinqualitylabelsall models 1nw9, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURE OF CASPASE-9 IN AN INHIBITORY COMPLEX WITH XIAP-BIR3

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 ZN 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 Mon Nov 12 18:26:33 2007