1rwk
From Proteopedia
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| - | [[Image:1rwk.gif|left|200px]] | + | [[Image:1rwk.gif|left|200px]] |
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| - | '''Crystal structure of human caspase-1 in complex with 3-(2-mercapto-acetylamino)-4-oxo-pentanoic acid''' | + | {{Structure |
| + | |PDB= 1rwk |SIZE=350|CAPTION= <scene name='initialview01'>1rwk</scene>, resolution 2.30Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=158:3-(2-MERCAPTO-ACETYLAMINO)-4-OXO-PENTANOIC ACID'>158</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] | ||
| + | |GENE= CASP1, IL1BC, IL1BCE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of human caspase-1 in complex with 3-(2-mercapto-acetylamino)-4-oxo-pentanoic acid''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1RWK is a [ | + | 1RWK is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RWK OCA]. |
==Reference== | ==Reference== | ||
| - | Structural analysis of caspase-1 inhibitors derived from Tethering., O'Brien T, Fahr BT, Sopko MM, Lam JW, Waal ND, Raimundo BC, Purkey HE, Pham P, Romanowski MJ, Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 May 1;61(Pt, 5):451-8. Epub 2005 Apr 9. PMID:[http:// | + | Structural analysis of caspase-1 inhibitors derived from Tethering., O'Brien T, Fahr BT, Sopko MM, Lam JW, Waal ND, Raimundo BC, Purkey HE, Pham P, Romanowski MJ, Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 May 1;61(Pt, 5):451-8. Epub 2005 Apr 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16511067 16511067] |
[[Category: Caspase-1]] | [[Category: Caspase-1]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: protein-small molecule inhibitor complex]] | [[Category: protein-small molecule inhibitor complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:57:09 2008'' |
Revision as of 11:57, 20 March 2008
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| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | CASP1, IL1BC, IL1BCE (Homo sapiens) | ||||||
| Activity: | Caspase-1, with EC number 3.4.22.36 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human caspase-1 in complex with 3-(2-mercapto-acetylamino)-4-oxo-pentanoic acid
Overview
Caspase-1 is a key endopeptidase responsible for the post-translational processing of the IL-1beta and IL-18 cytokines and small-molecule inhibitors that modulate the activity of this enzyme are predicted to be important therapeutic treatments for many inflammatory diseases. A fragment-assembly approach, accompanied by structural analysis, was employed to generate caspase-1 inhibitors. With the aid of Tethering with extenders (small molecules that bind to the active-site cysteine and contain a free thiol), two novel fragments that bound to the active site and made a disulfide bond with the extender were identified by mass spectrometry. Direct linking of each fragment to the extender generated submicromolar reversible inhibitors that significantly reduced secretion of IL-1beta but not IL-6 from human peripheral blood mononuclear cells. Thus, Tethering with extenders facilitated rapid identification and synthesis of caspase-1 inhibitors with cell-based activity and subsequent structural analyses provided insights into the enzyme's ability to accommodate different inhibitor-binding modes in the active site.
About this Structure
1RWK is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural analysis of caspase-1 inhibitors derived from Tethering., O'Brien T, Fahr BT, Sopko MM, Lam JW, Waal ND, Raimundo BC, Purkey HE, Pham P, Romanowski MJ, Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 May 1;61(Pt, 5):451-8. Epub 2005 Apr 9. PMID:16511067
Page seeded by OCA on Thu Mar 20 13:57:09 2008
