1nms: Difference between revisions
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|PDB= 1nms |SIZE=350|CAPTION= <scene name='initialview01'>1nms</scene>, resolution 1.70Å | |PDB= 1nms |SIZE=350|CAPTION= <scene name='initialview01'>1nms</scene>, resolution 1.70Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=161:5-[4-(1-CARBOXYMETHYL-2-OXO-PROPYLCARBAMOYL)-BENZYLSULFAMOYL]-2-HYDROXY-BENZOIC ACID'>161</scene> | |LIGAND= <scene name='pdbligand=161:5-[4-(1-CARBOXYMETHYL-2-OXO-PROPYLCARBAMOYL)-BENZYLSULFAMOYL]-2-HYDROXY-BENZOIC+ACID'>161</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1nme|1NME]], [[1nmq|1NMQ]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nms OCA], [http://www.ebi.ac.uk/pdbsum/1nms PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1nms RCSB]</span> | |||
}} | }} | ||
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[[Category: Simmons, R L.]] | [[Category: Simmons, R L.]] | ||
[[Category: Wiesmann, C.]] | [[Category: Wiesmann, C.]] | ||
[[Category: caspase-3]] | [[Category: caspase-3]] | ||
[[Category: inhibitor]] | [[Category: inhibitor]] | ||
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[[Category: tether]] | [[Category: tether]] | ||
''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 22:32:32 2008'' | ||
Revision as of 22:32, 30 March 2008
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| , resolution 1.70Å | |||||||
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| Ligands: | |||||||
| Related: | 1NME, 1NMQ
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Caspase-3 tethered to irreversible inhibitor
OverviewOverview
Cysteine aspartyl protease-3 (caspase-3) is a mediator of apoptosis and a therapeutic target for a wide range of diseases. Using a dynamic combinatorial technology, 'extended tethering', we identified unique nonpeptidic inhibitors for this enzyme. Extended tethering allowed the identification of ligands that bind to discrete regions of caspase-3 and also helped direct the assembly of these ligands into small-molecule inhibitors. We first designed a small-molecule 'extender' that irreversibly alkylates the cysteine residue of caspase-3 and also contains a thiol group. The modified protein was then screened against a library of disulfide-containing small-molecule fragments. Mass-spectrometry was used to identify ligands that bind noncovalently to the protein and that also form a disulfide linkage with the extender. Linking the selected fragments with binding elements from the extenders generates reversible, tight-binding molecules that are druglike and distinct from known inhibitors. One molecule derived from this approach inhibited apoptosis in cells.
About this StructureAbout this Structure
1NMS is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
In situ assembly of enzyme inhibitors using extended tethering., Erlanson DA, Lam JW, Wiesmann C, Luong TN, Simmons RL, DeLano WL, Choong IC, Burdett MT, Flanagan WM, Lee D, Gordon EM, O'Brien T, Nat Biotechnol. 2003 Mar;21(3):308-14. Epub 2003 Feb 3. PMID:12563278
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