2fqq
From Proteopedia
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|PDB= 2fqq |SIZE=350|CAPTION= <scene name='initialview01'>2fqq</scene>, resolution 3.30Å | |PDB= 2fqq |SIZE=350|CAPTION= <scene name='initialview01'>2fqq</scene>, resolution 3.30Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=F1G:1-METHYL-3-TRIFLUOROMETHYL-1H-THIENO[2,3-C]PYRAZOLE-5-CARBOXYLIC ACID (2-MERCAPTO-ETHYL)-AMIDE'>F1G</scene> | + | |LIGAND= <scene name='pdbligand=F1G:1-METHYL-3-TRIFLUOROMETHYL-1H-THIENO[2,3-C]PYRAZOLE-5-CARBOXYLIC+ACID+(2-MERCAPTO-ETHYL)-AMIDE'>F1G</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Caspase-1 Caspase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.36 3.4.22.36] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-1 Caspase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.36 3.4.22.36] </span> |
|GENE= CASP1, IL1BC, IL1BCE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CASP1, IL1BC, IL1BCE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1sc1|1sc1]], [[1sc3|1sc3]], [[1sc4|1sc4]], [[2fqr|2FQR]], [[2fqs|2FQS]], [[2fqu|2FQU]], [[2fqv|2FQV]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fqq OCA], [http://www.ebi.ac.uk/pdbsum/2fqq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fqq RCSB]</span> | ||
}} | }} | ||
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[[Category: Scheer, J M.]] | [[Category: Scheer, J M.]] | ||
[[Category: Wells, J A.]] | [[Category: Wells, J A.]] | ||
| - | [[Category: F1G]] | ||
[[Category: allosteric inhibitor]] | [[Category: allosteric inhibitor]] | ||
[[Category: caspase]] | [[Category: caspase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:06:30 2008'' |
Revision as of 00:06, 31 March 2008
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| , 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 | ||||||
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
Overview
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.
About this Structure
2FQQ is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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