| Literature DB >> 11257230 |
J Chai1, E Shiozaki, S M Srinivasula, Q Wu, P Datta, E S Alnemri, Y Shi, P Dataa.
Abstract
The inhibitor of apoptosis (IAP) proteins suppress cell death by inhibiting the catalytic activity of caspases. Here we present the crystal structure of caspase-7 in complex with a potent inhibitory fragment from XIAP at 2.45 A resolution. An 18-residue XIAP peptide binds the catalytic groove of caspase-7, making extensive contacts to the residues that are essential for its catalytic activity. Strikingly, despite a reversal of relative orientation, a subset of interactions between caspase-7 and XIAP closely resemble those between caspase-7 and its tetrapeptide inhibitor DEVD-CHO. Our biochemical and structural analyses reveal that the BIR domains are dispensable for the inhibition of caspase-3 and -7. This study provides a structural basis for the design of the next-generation caspase inhibitors.Entities:
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Year: 2001 PMID: 11257230 DOI: 10.1016/s0092-8674(01)00272-0
Source DB: PubMed Journal: Cell ISSN: 0092-8674 Impact factor: 41.582