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[[Image:3qw6.png|left|200px]]
==Crystal structure of the protease domain of Botulinum Neurotoxin Serotype A with a peptide inhibitor RYGC==
<StructureSection load='3qw6' size='340' side='right' caption='[[3qw6]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3qw6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum_a_str._hall Clostridium botulinum a str. hall]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QW6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bwi|3bwi]], [[3c88|3c88]], [[3c89|3c89]], [[3c8a|3c8a]], [[3c8b|3c8b]], [[3dda|3dda]], [[3ddb|3ddb]], [[3qw5|3qw5]], [[3qw7|3qw7]], [[3qw8|3qw8]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">botA, CBO0806, CLC_0862 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=441771 Clostridium botulinum A str. Hall])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3qw6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qw6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qw6 RCSB], [http://www.ebi.ac.uk/pdbsum/3qw6 PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC(50) of 0.9 microM and a K(i) of 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features.


{{STRUCTURE_3qw6|  PDB=3qw6  |  SCENE=  }}
Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling.,Kumar G, Kumaran D, Ahmed SA, Swaminathan S Acta Crystallogr D Biol Crystallogr. 2012 May;68(Pt 5):511-20. Epub 2012 Apr 17. PMID:22525749<ref>PMID:22525749</ref>


===Crystal structure of the protease domain of Botulinum Neurotoxin Serotype A with a peptide inhibitor RYGC===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
{{ABSTRACT_PUBMED_22525749}}
== References ==
 
<references/>
==About this Structure==
__TOC__
[[3qw6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum_a_str._hall Clostridium botulinum a str. hall]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QW6 OCA].
</StructureSection>
[[Category: Bontoxilysin]]
[[Category: Bontoxilysin]]
[[Category: Clostridium botulinum a str. hall]]
[[Category: Clostridium botulinum a str. hall]]
[[Category: Kumaran, D.]]
[[Category: Kumaran, D]]
[[Category: Swaminathan, S.]]
[[Category: Swaminathan, S]]
[[Category: Bio-warfare agent]]
[[Category: Bio-warfare agent]]
[[Category: Endopeptidase]]
[[Category: Endopeptidase]]

Revision as of 16:05, 9 December 2014

Crystal structure of the protease domain of Botulinum Neurotoxin Serotype A with a peptide inhibitor RYGCCrystal structure of the protease domain of Botulinum Neurotoxin Serotype A with a peptide inhibitor RYGC

Structural highlights

3qw6 is a 2 chain structure with sequence from Clostridium botulinum a str. hall. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
NonStd Res:
Gene:botA, CBO0806, CLC_0862 (Clostridium botulinum A str. Hall)
Activity:Bontoxilysin, with EC number 3.4.24.69
Resources:FirstGlance, OCA, RCSB, PDBsum

Publication Abstract from PubMed

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC(50) of 0.9 microM and a K(i) of 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features.

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling.,Kumar G, Kumaran D, Ahmed SA, Swaminathan S Acta Crystallogr D Biol Crystallogr. 2012 May;68(Pt 5):511-20. Epub 2012 Apr 17. PMID:22525749[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Kumar G, Kumaran D, Ahmed SA, Swaminathan S. Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling. Acta Crystallogr D Biol Crystallogr. 2012 May;68(Pt 5):511-20. Epub 2012 Apr 17. PMID:22525749 doi:http://dx.doi.org/10.1107/S0907444912003551

3qw6, resolution 1.60Å

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