1rwn
From Proteopedia
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|PDB= 1rwn |SIZE=350|CAPTION= <scene name='initialview01'>1rwn</scene>, resolution 2.00Å | |PDB= 1rwn |SIZE=350|CAPTION= <scene name='initialview01'>1rwn</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=4QB:3-{2-ETHYL-6-[4-(QUINOXALIN-2-YLAMINO)-BENZOYLAMINO]-HEXANOYLAMINO}-4-OXO-BUTYRIC ACID'>4QB</scene> | + | |LIGAND= <scene name='pdbligand=4QB:3-{2-ETHYL-6-[4-(QUINOXALIN-2-YLAMINO)-BENZOYLAMINO]-HEXANOYLAMINO}-4-OXO-BUTYRIC+ACID'>4QB</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=[[1ice|1ICE]], [[1bmq|1BMQ]], [[1ibc|1IBC]], [[1rwk|1RWK]], [[1rwm|1RWM]], [[1rwo|1RWO]], [[1rwp|1RWP]], [[1rwv|1RWV]], [[1rww|1RWW]], [[1rwx|1RWX]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rwn OCA], [http://www.ebi.ac.uk/pdbsum/1rwn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1rwn RCSB]</span> | ||
}} | }} | ||
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[[Category: Fahr, B T.]] | [[Category: Fahr, B T.]] | ||
[[Category: Romanowski, M J.]] | [[Category: Romanowski, M J.]] | ||
| - | [[Category: 4QB]] | ||
[[Category: protein-small molecule inhibitor complex]] | [[Category: protein-small molecule inhibitor complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:33:56 2008'' |
Revision as of 20:33, 30 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | CASP1, IL1BC, IL1BCE (Homo sapiens) | ||||||
| Activity: | Caspase-1, with EC number 3.4.22.36 | ||||||
| Related: | 1ICE, 1BMQ, 1IBC, 1RWK, 1RWM, 1RWO, 1RWP, 1RWV, 1RWW, 1RWX
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human caspase-1 in complex with 3-{2-ethyl-6-[4-(quinoxalin-2-ylamino)-benzoylamino]-hexanoylamino}-4-oxo-butyric 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
1RWN 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 Sun Mar 30 23:33:56 2008
