1I3O

CRYSTAL STRUCTURE OF THE COMPLEX OF XIAP-BIR2 AND CASPASE 3

Summary for 1I3O

• Entry DOI: 10.2210/pdb1i3o/pdb
• Related: 1C9Q 1PAU
• Descriptor: CASPASE 3, BACULOVIRAL IAP REPEAT-CONTAINING PROTEIN 4, ZINC ION, ... (5 entities in total)
• Functional Keywords: complex, iap, caspase, apoptosis
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P42574 P42574 P98170
• Total number of polymer chains: 6
• Total formula weight: 93536.04

Authors

Riedl, S.J.,Renatus, M.,Schwarzenbacher, R.,Zhou, Q.,Sun, C.,Fesik, S.W.,Liddington, R.C.,Salvesen, G.S. (deposition date: 2001-02-15, release date: 2001-03-21, Last modification date: 2023-08-09)

Primary citation

Riedl, S.J.,Renatus, M.,Schwarzenbacher, R.,Zhou, Q.,Sun, C.,Fesik, S.W.,Liddington, R.C.,Salvesen, G.S.
Structural basis for the inhibition of caspase-3 by XIAP.
Cell(Cambridge,Mass.), 104:791-800, 2001

PubMed Abstract: The molecular mechanism(s) that regulate apoptosis by caspase inhibition remain poorly understood. The main endogenous inhibitors are members of the IAP family and are exemplified by XIAP, which regulates the initiator caspase-9, and the executioner caspases-3 and -7. We report the crystal structure of the second BIR domain of XIAP (BIR2) in complex with caspase-3, at a resolution of 2.7 A, revealing the structural basis for inhibition. The inhibitor makes limited contacts through its BIR domain to the surface of the enzyme, and most contacts to caspase-3 originate from the N-terminal extension. This lies across the substrate binding cleft, but in reverse orientation compared to substrate binding. The mechanism of inhibition is due to a steric blockade prohibitive of substrate binding, and is distinct from the mechanism utilized by synthetic substrate analog inhibitors.

PubMed: 11257232
DOI: 10.1016/S0092-8674(01)00274-4

Experimental method

X-RAY DIFFRACTION (2.7 Å)