2ilp
From Proteopedia
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|PDB= 2ilp |SIZE=350|CAPTION= <scene name='initialview01'>2ilp</scene>, resolution 1.90Å | |PDB= 2ilp |SIZE=350|CAPTION= <scene name='initialview01'>2ilp</scene>, resolution 1.90Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=GB5:(2E)-3-(4-CHLOROPHENYL)-N-HYDROXYACRYLAMIDE'>GB5</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Bontoxilysin Bontoxilysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.69 3.4.24.69] </span> |
|GENE= botA, atx, bna ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum]) | |GENE= botA, atx, bna ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ilp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ilp OCA], [http://www.ebi.ac.uk/pdbsum/2ilp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ilp RCSB]</span> | ||
}} | }} | ||
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[[Category: Allen, K N.]] | [[Category: Allen, K N.]] | ||
[[Category: Silvaggi, N R.]] | [[Category: Silvaggi, N R.]] | ||
| - | [[Category: GB5]] | ||
| - | [[Category: PO4]] | ||
| - | [[Category: ZN]] | ||
[[Category: clostridium botulinum neurotoxin]] | [[Category: clostridium botulinum neurotoxin]] | ||
[[Category: protease inhibitor]] | [[Category: protease inhibitor]] | ||
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[[Category: type some]] | [[Category: type some]] | ||
| - | ''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 03:45:48 2008'' |
Revision as of 00:45, 31 March 2008
| |||||||
| , resolution 1.90Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | botA, atx, bna (Clostridium botulinum) | ||||||
| Activity: | Bontoxilysin, with EC number 3.4.24.69 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Clostridium botulinum Serotype A Light Chain inhibited by 4-chlorocinnamic hydroxamate
Overview
The potential for the use of Clostridial neurotoxins as bioweapons makes the development of small-molecule inhibitors of these deadly toxins a top priority. Recently, screening of a random hydroxamate library identified a small-molecule inhibitor of C. botulinum Neurotoxin Serotype A Light Chain (BoNT/A-LC), 4-chlorocinnamic hydroxamate, a derivative of which has been shown to have in vivo efficacy in mice and no toxicity. We describe the X-ray crystal structures of BoNT/A-LC in complexes with two potent small-molecule inhibitors. The structures of the enzyme with 4-chlorocinnamic hydroxamate or 2,4-dichlorocinnamic hydroxamate bound are compared to the structure of the enzyme complexed with L-arginine hydroxamate, an inhibitor with modest affinity. Taken together, this suite of structures provides surprising insights into the BoNT/A-LC active site, including unexpected conformational flexibility at the S1' site that changes the electrostatic environment of the binding pocket. Information gained from these structures will inform the design and optimization of more effective small-molecule inhibitors of BoNT/A-LC.
About this Structure
2ILP is a Single protein structure of sequence from Clostridium botulinum. Full crystallographic information is available from OCA.
Reference
Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain complexed with small-molecule inhibitors highlight active-site flexibility., Silvaggi NR, Boldt GE, Hixon MS, Kennedy JP, Tzipori S, Janda KD, Allen KN, Chem Biol. 2007 May;14(5):533-42. PMID:17524984
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