3QNW

Caspase-6 in complex with Z-VAD-FMK inhibitor

Summary for 3QNW

• Entry DOI: 10.2210/pdb3qnw/pdb
• Related: 3P45 3P4U
• Related PRD ID: PRD_000338
• Descriptor: Caspase-6, Z-VAD-FMK, ... (4 entities in total)
• Functional Keywords: cysteine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P55212 P55212
• Total number of polymer chains: 11
• Total formula weight: 119011.01

Authors

Mueller, I.,Lamers, M.,Ritchie, A.,Park, H.,Dominguez, C.,Munoz, I.,Maillard, M.,Kiselyov, A. (deposition date: 2011-02-09, release date: 2011-09-21, Last modification date: 2024-11-06)

Primary citation

Muller, I.,Lamers, M.B.,Ritchie, A.J.,Dominguez, C.,Munoz-Sanjuan, I.,Kiselyov, A.
Structure of human caspase-6 in complex with Z-VAD-FMK: New peptide binding mode observed for the non-canonical caspase conformation.
Bioorg.Med.Chem.Lett., 21:5244-5247, 2011

PubMed Abstract: Caspase-6 is a cysteine protease implicated in neuronal survival and apoptosis. Deregulation of caspase-6 activity was linked to several neurodegenerative disorders including Alzheimer's and Huntington's Diseases. Several recent studies on the structure of caspase-6 feature the caspase-6 zymogen, mature apo-caspase-6 as well as the Ac-VEID-CHO peptide complex. All structures share the same typical dimeric caspase conformation. However, mature apo-caspase-6 crystallized at low pH revealed a novel, non-canonical inactive caspase conformation speculated to represent a latent state of the enzyme suitable for the design of allosteric inhibitors. In this treatise we present the structure of caspase-6 in the non-canonical inactive enzyme conformation bound to the irreversible inhibitor Z-VAD-FMK. The complex features a unique peptide binding mode not observed previously.

PubMed: 21820899
DOI: 10.1016/j.bmcl.2011.07.041

Experimental method

X-RAY DIFFRACTION (2.65 Å)