2imb
From Proteopedia
(New page: 200px<br /><applet load="2imb" size="450" color="white" frame="true" align="right" spinBox="true" caption="2imb, resolution 2.41Å" /> '''Clostridium botulinu...) |
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| - | [[Image:2imb.jpg|left|200px]]<br /><applet load="2imb" size=" | + | [[Image:2imb.jpg|left|200px]]<br /><applet load="2imb" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2imb, resolution 2.41Å" /> | caption="2imb, resolution 2.41Å" /> | ||
'''Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by L-arginine hydroxamate'''<br /> | '''Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by L-arginine hydroxamate'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2IMB 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 and AHL as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 2IMB 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> and <scene name='pdbligand=AHL:'>AHL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=2IMB OCA]. |
==Reference== | ==Reference== | ||
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[[Category: substrate switching]] | [[Category: substrate switching]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:00:44 2008'' |
Revision as of 13:00, 23 January 2008
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Clostridium botulinum Neurotoxin Serotype A Light Chain Inhibited by L-arginine 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
2IMB is a Single protein structure of sequence from Clostridium botulinum with and as ligands. 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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