3OD5

Crystal structure of active caspase-6 bound with Ac-VEID-CHO

Summary for 3OD5

• Entry DOI: 10.2210/pdb3od5/pdb
• Related: 3NR2
• Related PRD ID: PRD_000976
• Descriptor: Caspase-6, peptide aldehyde inhibitor AC-VEID-CHO, CACODYLATE ION, ... (4 entities in total)
• Functional Keywords: caspase domain, apoptotic protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P55212
• Total number of polymer chains: 4
• Total formula weight: 66174.27

Authors

Wang, X.-J.,Liu, X.,Wang, K.-T.,Cao, Q.,Su, X.-D. (deposition date: 2010-08-11, release date: 2010-10-27, Last modification date: 2024-11-13)

Primary citation

Wang, X.-J.,Cao, Q.,Liu, X.,Wang, K.-T.,Mi, W.,Zhang, Y.,Li, L.-F.,Leblanc, A.C.,Su, X.-D.
Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation
Embo Rep., 11:841-847, 2010

PubMed Abstract: Dimeric effectors caspase 3 and caspase 7 are activated by initiator caspase processing. In this study, we report the crystal structures of effector caspase 6 (CASP6) zymogen and N-Acetyl-Val-Glu-Ile-Asp-al-inhibited CASP6. Both of these forms of CASP6 have a dimeric structure, and in CASP6 zymogen the intersubunit cleavage site (190)TEVD(193) is well structured and inserts into the active site. This positions residue Asp 193 to be easily attacked by the catalytic residue Cys 163. We demonstrate biochemically that intramolecular cleavage at Asp 193 is a prerequisite for CASP6 self-activation and that this activation mechanism is dependent on the length of the L2 loop. Our results indicate that CASP6 can be activated and regulated through intramolecular self-cleavage.

PubMed: 20890311
DOI: 10.1038/embor.2010.141

Experimental method

X-RAY DIFFRACTION (1.6 Å)