2imb: Difference between revisions
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'''Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by L-arginine hydroxamate''' | {{Structure | ||
|PDB= 2imb |SIZE=350|CAPTION= <scene name='initialview01'>2imb</scene>, resolution 2.41Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=AHL:N-HYDROXY-L-ARGININAMIDE'>AHL</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] | |||
|GENE= botA, atx, bna ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum]) | |||
}} | |||
'''Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by L-arginine hydroxamate''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2IMB is a [ | 2IMB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IMB OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17524984 17524984] | ||
[[Category: Bontoxilysin]] | [[Category: Bontoxilysin]] | ||
[[Category: Clostridium botulinum]] | [[Category: Clostridium botulinum]] | ||
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[[Category: AHL]] | [[Category: AHL]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: clostridium botulinum neurotoxin serotype | [[Category: clostridium botulinum neurotoxin serotype some]] | ||
[[Category: protease | [[Category: protease inhibitor]] | ||
[[Category: substrate specificity]] | [[Category: substrate specificity]] | ||
[[Category: substrate switching]] | [[Category: substrate switching]] | ||
''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 17:31:05 2008'' | ||
Revision as of 18:31, 20 March 2008
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| , resolution 2.41Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | botA, atx, bna (Clostridium botulinum) | ||||||
| Activity: | Bontoxilysin, with EC number 3.4.24.69 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by L-arginine hydroxamate
OverviewOverview
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 StructureAbout this Structure
2IMB is a Single protein structure of sequence from Clostridium botulinum. Full crystallographic information is available from OCA.
ReferenceReference
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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