2a97
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The seven serologically distinct Clostridium botulinum neurotoxins (BoNTs, A-G) are zinc endopeptidases which block the neurotransmitter release by, cleaving one of the three proteins of the soluble, N-ethylmaleimide-sensitive-factor attachment protein receptor complex, (SNARE complex) essential for the fusion of vesicles containing, neurotransmitters with target membranes. These metallopeptidases exhibit, unique specificity for the substrates and peptide bonds they cleave., Development of countermeasures and therapeutics for BoNTs is a priority, because of their extreme toxicity and potential misuse as biowarfare, agents. Though they share sequence homology and structural similarity, the, structural information on each one of them is required to understand the, mechanism of action of all ... | + | The seven serologically distinct Clostridium botulinum neurotoxins (BoNTs, A-G) are zinc endopeptidases which block the neurotransmitter release by, cleaving one of the three proteins of the soluble, N-ethylmaleimide-sensitive-factor attachment protein receptor complex, (SNARE complex) essential for the fusion of vesicles containing, neurotransmitters with target membranes. These metallopeptidases exhibit, unique specificity for the substrates and peptide bonds they cleave., Development of countermeasures and therapeutics for BoNTs is a priority, because of their extreme toxicity and potential misuse as biowarfare, agents. Though they share sequence homology and structural similarity, the, structural information on each one of them is required to understand the, mechanism of action of all of them because of their specificity., Unraveling the mechanism will help in the ultimate goal of developing, inhibitors as antibotulinum drugs for the toxins. Here, we report the, high-resolution structure of active BoNT/F catalytic domain in two crystal, forms. The structure was exploited for modeling the substrate binding and, identifying the S1' subsite and the putative exosites which are different, from BoNT/A or BoNT/B. The orientation of docking of the substrate at the, active site is consistent with the experimental BoNT/A-LC:SNAP-25 peptide, model and our proposed model for BoNT/E-LC:SNAP-25. |
==About this Structure== | ==About this Structure== | ||
| - | 2A97 is a | + | 2A97 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 CD 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] Structure known Active Sites: CDA, CDB, CDC, CDD, CDE, CDF, ZNA and ZNB. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2A97 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: clostridium botulinum neurotoxin serotype f; light chain; catalytic domain; x-ray; crystal structure; zinc endopeptidase]] | [[Category: clostridium botulinum neurotoxin serotype f; light chain; catalytic domain; x-ray; crystal structure; zinc endopeptidase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:22:50 2007'' |
Revision as of 12:17, 5 November 2007
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Crystal structure of catalytic domain of Clostridium botulinum neurotoxin serotype F
Overview
The seven serologically distinct Clostridium botulinum neurotoxins (BoNTs, A-G) are zinc endopeptidases which block the neurotransmitter release by, cleaving one of the three proteins of the soluble, N-ethylmaleimide-sensitive-factor attachment protein receptor complex, (SNARE complex) essential for the fusion of vesicles containing, neurotransmitters with target membranes. These metallopeptidases exhibit, unique specificity for the substrates and peptide bonds they cleave., Development of countermeasures and therapeutics for BoNTs is a priority, because of their extreme toxicity and potential misuse as biowarfare, agents. Though they share sequence homology and structural similarity, the, structural information on each one of them is required to understand the, mechanism of action of all of them because of their specificity., Unraveling the mechanism will help in the ultimate goal of developing, inhibitors as antibotulinum drugs for the toxins. Here, we report the, high-resolution structure of active BoNT/F catalytic domain in two crystal, forms. The structure was exploited for modeling the substrate binding and, identifying the S1' subsite and the putative exosites which are different, from BoNT/A or BoNT/B. The orientation of docking of the substrate at the, active site is consistent with the experimental BoNT/A-LC:SNAP-25 peptide, model and our proposed model for BoNT/E-LC:SNAP-25.
About this Structure
2A97 is a Single protein structure of sequence from Clostridium botulinum with ZN and CD as ligands. Active as Bontoxilysin, with EC number 3.4.24.69 Structure known Active Sites: CDA, CDB, CDC, CDD, CDE, CDF, ZNA and ZNB. Full crystallographic information is available from OCA.
Reference
Structural analysis of botulinum neurotoxin serotype F light chain: implications on substrate binding and inhibitor design., Agarwal R, Binz T, Swaminathan S, Biochemistry. 2005 Sep 6;44(35):11758-65. PMID:16128577
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