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2fqq

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2fqq, resolution 3.30Å ()
Ligands:
Gene: CASP1, IL1BC, IL1BCE (Homo sapiens)
Activity: Caspase-1, with EC number 3.4.22.36
Related: 1sc1, 1sc3, 1sc4, 2fqr, 2fqs, 2fqu, 2fqv
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Crystal structure of human caspase-1 (Cys285->Ala, Cys362->Ala, Cys364->Ala, Cys397->Ala) in complex with 1-methyl-3-trifluoromethyl-1H-thieno[2,3-c]pyrazole-5-carboxylic acid (2-mercapto-ethyl)-amide

Publication Abstract from PubMed

We present a common allosteric mechanism for control of inflammatory and apoptotic caspases. Highly specific thiol-containing inhibitors of the human inflammatory caspase-1 were identified by using disulfide trapping, a method for site-directed small-molecule discovery. These compounds became trapped by forming a disulfide bond with a cysteine residue in the cavity at the dimer interface approximately 15 A away from the active site. Mutational and structural analysis uncovered a linear circuit of functional residues that runs from one active site through the allosteric cavity and into the second active site. Kinetic analysis revealed robust positive cooperativity not seen in other endopeptidases. Recently, disulfide trapping identified a similar small-molecule site and allosteric transition in the apoptotic caspase-7 that shares only a 23% sequence identity with caspase-1. Together, these studies show a general small-molecule-binding site for functionally reversing the zymogen activation of caspases and suggest a common regulatory site for the allosteric control of inflammation and apoptosis.

A common allosteric site and mechanism in caspases., Scheer JM, Romanowski MJ, Wells JA, Proc Natl Acad Sci U S A. 2006 May 16;103(20):7595-600. Epub 2006 May 8. PMID:16682620

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2fqq is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Scheer JM, Romanowski MJ, Wells JA. A common allosteric site and mechanism in caspases. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7595-600. Epub 2006 May 8. PMID:16682620

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