1K88

Crystal structure of procaspase-7

Summary for 1K88

• Entry DOI: 10.2210/pdb1k88/pdb
• Related: 1I51 1K86
• Descriptor: procaspase-7 (2 entities in total)
• Functional Keywords: procaspase activation, apoptosis, protease, substrate binding
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P55210
• Total number of polymer chains: 2
• Total formula weight: 57475.34

Authors

Chai, J.,Wu, Q.,Shiozaki, E.,Srinivasa, S.M.,Alnemri, E.S.,Shi, Y. (deposition date: 2001-10-23, release date: 2001-11-21, Last modification date: 2024-02-07)

Primary citation

Chai, J.,Wu, Q.,Shiozaki, E.,Srinivasula, S.M.,Alnemri, E.S.,Shi, Y.
Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding
Cell(Cambridge,Mass.), 107:399-407, 2001

PubMed Abstract: Apoptosis is primarily executed by active caspases, which are derived from the inactive procaspase zymogens through proteolytic cleavage. Here we report the crystal structures of a caspase zymogen, procaspase-7, and an active caspase-7 without any bound inhibitors. Compared to the inhibitor-bound caspase-7, procaspase-7 zymogen exhibits significant structural differences surrounding the catalytic cleft, which precludes the formation of a productive conformation. Proteolytic cleavage between the large and small subunits allows rearrangement of essential loops in the active site, priming active caspase-7 for inhibitor/substrate binding. Strikingly, binding by inhibitors causes a 180 degrees flipping of the N terminus in the small subunit, which interacts with and stabilizes the catalytic cleft. These analyses reveal the structural mechanisms of caspase activation and demonstrate that the inhibitor/substrate binding is a process of induced fit.

PubMed: 11701129
DOI: 10.1016/S0092-8674(01)00544-X

Experimental method

X-RAY DIFFRACTION (2.7 Å)