2imc
From Proteopedia
(New page: 200px<br /><applet load="2imc" size="450" color="white" frame="true" align="right" spinBox="true" caption="2imc, resolution 2.00Å" /> '''Clostridium botulinu...) |
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| - | [[Image:2imc.jpg|left|200px]]<br /><applet load="2imc" size=" | + | [[Image:2imc.jpg|left|200px]]<br /><applet load="2imc" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2imc, resolution 2.00Å" /> | caption="2imc, resolution 2.00Å" /> | ||
'''Clostridium botulinum Neurotoxin Serotype A Light Chain, Residues 1-424'''<br /> | '''Clostridium botulinum Neurotoxin Serotype A Light Chain, Residues 1-424'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2IMC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 2IMC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IMC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: substrate specificity]] | [[Category: substrate specificity]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:00:45 2008'' |
Revision as of 13:00, 23 January 2008
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Clostridium botulinum Neurotoxin Serotype A Light Chain, Residues 1-424
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
2IMC is a Single protein structure of sequence from Clostridium botulinum with as ligand. Active as Bontoxilysin, with EC number 3.4.24.69 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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