3qw8

From Proteopedia

(Difference between revisions)

Revision as of 06:54, 5 August 2016

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

Structural highlights

3qw8 is a 2 chain structure with sequence from Clobh. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
NonStd Res:
Related:	3bwi, 3c88, 3c89, 3c8a, 3c8b, 3dda, 3ddb, 3qw5, 3qw6, 3qw7
Gene:	botA, CBO0806, CLC_0862 (CLOBH)
Activity:	Bontoxilysin, with EC number 3.4.24.69
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BXA1_CLOBH] Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure.

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

↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3qw8"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the protease domain of Botulinum Neurotoxin Serotype A with a peptide inhibitor CRGC==
 <StructureSection load='3qw8' size='340' side='right' caption='[[3qw8]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3qw8]] 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=3QW8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QW8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3qw8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Clobh Clobh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QW8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QW8 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <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]], [[3qw6|3qw6]], [[3qw7|3qw7]]</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='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 CLOBH])</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=3qw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qw8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qw8 RCSB], [http://www.ebi.ac.uk/pdbsum/3qw8 PDBsum]</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=3qw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qw8 OCA], [http://pdbe.org/3qw8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qw8 RCSB], [http://www.ebi.ac.uk/pdbsum/3qw8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qw8 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3qw8" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Botulinum neurotoxin|Botulinum neurotoxin]]
 == References ==
 <references/>
@@ Line 25: / Line 30: @@
 </StructureSection>
 [[Category: Bontoxilysin]]
-[[Category: Clostridium botulinum a str. hall]]
+[[Category: Clobh]]
 [[Category: Kumaran, D]]
 [[Category: Swaminathan, S]]

3qw8

From Proteopedia

Revision as of 06:54, 5 August 2016

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

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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