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| {{STRUCTURE_2imc| PDB=2imc | SCENE= }} | | {{STRUCTURE_2imc| PDB=2imc | SCENE= }} |
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| '''Clostridium botulinum Neurotoxin Serotype A Light Chain, Residues 1-424'''
| | ===Clostridium botulinum Neurotoxin Serotype A Light Chain, Residues 1-424=== |
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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_17524984}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17524984 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17524984}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Protease inhibitor]] | | [[Category: Protease inhibitor]] |
| [[Category: Substrate specificity]] | | [[Category: Substrate specificity]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:39:11 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 11:59:50 2008'' |