Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

4EJF

Allosteric peptides that bind to a caspase zymogen and mediate caspase tetramerization

Summary for 4EJF
Entry DOI10.2210/pdb4ejf/pdb
DescriptorCaspase-6, phage-derived peptide 419, PHOSPHATE ION, ... (4 entities in total)
Functional Keywordscaspase-6, zymogen, c163a, caspase, protease, hydrolase
Biological sourceHomo sapiens (human)
More
Cellular locationCytoplasm: P55212
Total number of polymer chains8
Total formula weight137342.77
Authors
Murray, J.M. (deposition date: 2012-04-06, release date: 2012-06-20, Last modification date: 2023-09-13)
Primary citationStanger, K.,Steffek, M.,Zhou, L.,Pozniak, C.D.,Quan, C.,Franke, Y.,Tom, J.,Tam, C.,Elliott, J.M.,Lewcock, J.W.,Zhang, Y.,Murray, J.,Hannoush, R.N.
Allosteric peptides bind a caspase zymogen and mediate caspase tetramerization.
Nat.Chem.Biol., 8:655-660, 2012
Cited by
PubMed Abstract: The caspases are a family of cytosolic proteases with essential roles in inflammation and apoptosis. Drug discovery efforts have focused on developing molecules directed against the active sites of caspases, but this approach has proved challenging and has not yielded any approved therapeutics. Here we describe a new strategy for generating inhibitors of caspase-6, a potential therapeutic target in neurodegenerative disorders, by screening against its zymogen form. Using phage display to discover molecules that bind the zymogen, we report the identification of a peptide that specifically impairs the function of caspase-6 in vitro and in neuronal cells. Remarkably, the peptide binds at a tetramerization interface that is uniquely present in zymogen caspase-6, rather than binding into the active site, and acts via a new allosteric mechanism that promotes caspase tetramerization. Our data illustrate that screening against the zymogen holds promise as an approach for targeting caspases in drug discovery.
PubMed: 22683611
DOI: 10.1038/nchembio.967
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.6465 Å)
Structure validation

227561

PDB entries from 2024-11-20

PDB statisticsPDBj update infoContact PDBjnumon