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Cell. 2001 Mar 9;104(5):769-80.

Structural basis of caspase-7 inhibition by XIAP.

Author information

1
Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.

Erratum in

  • Cell 2001 Nov 2;107(3):409. Dataa P [corrected to Datta P].

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.

PMID:
11257230
DOI:
10.1016/s0092-8674(01)00272-0
[Indexed for MEDLINE]
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