Structural basis of caspase-7 inhibition by XIAP

Cell. 2001 Mar 9;104(5):769-80. doi: 10.1016/s0092-8674(01)00272-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / physiology
  • Carrier Proteins*
  • Caspase 7
  • Caspases / chemistry*
  • Caspases / genetics
  • Caspases / metabolism*
  • Catalytic Domain
  • Mitochondrial Proteins*
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • X-Linked Inhibitor of Apoptosis Protein


  • Carrier Proteins
  • Mitochondrial Proteins
  • Proteins
  • X-Linked Inhibitor of Apoptosis Protein
  • Caspase 7
  • Caspases

Associated data

  • PDB/1I51