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4iqp

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Revision as of 23:34, 5 August 2016

Crystal Structure of HCRA-W1266A

Structural highlights

4iqp is a 1 chain structure with sequence from "bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3fuo
Gene:	atx, bna, botA, Botulinum neurotoxin type A receptor binding domain ("Bacillus botulinus" van Ermengem 1896)
Activity:	Bontoxilysin, with EC number 3.4.24.69
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BXA1_CLOBO] 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

The need for a vaccine against botulism has increased since the discontinuation of the Pentavalent (ABCDE) Botulinum Toxoid Vaccine by the Centers for Disease Control and Prevention. The Botulinum toxins (BoNTs) are the primary virulence factors and vaccine components against botulism. BoNTs comprise three domains which are involved in catalysis (LC), translocation (HCT) and host receptor binding (HCR). Recombinant HCR subunits have been used to develop the next generation of BoNT vaccine. Using structural studies and the known entry properties of the BoNT/A, an HCR subunit vaccine against BoNT/A was designed that contained the point mutation W1266A within the ganglioside binding pocket. HCR/A(W1266A) did not enter primary neurons and the crystal structure of HCR/A(W1266A) was virtually identical to wild type HCR/A. Using a mouse model, experiments were performed using a high dose vaccine and a low dose vaccine. At high vaccine dose, HCR/A and HCR/A(W1266A) elicited a protective immune response to BoNT/A challenge. At the low dose vaccination, HCR/A(W1266A) was a more protective vaccine than HCR/A. alpha-HCR IgG titers correlated with protection from BoNT challenge, although titers to block HCR/A entry were greater in serum in HCR/A vaccinated mice relative to HCR/A(W1266A) vaccinated mice. This study shows that removal of receptor binding capacity enhances potency of the subunit HCR vaccine. Vaccines that lack receptor binding capacity have the added property of limited off-target toxicity.

Enhancing the Protective Immune Response against Botulism.,Przedpelski A, Tepp WH, Kroken AR, Fu Z, Kim JJ, Johnson EA, Barbieri JT Infect Immun. 2013 May 13. PMID:23670557^[1]

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

References

↑ Przedpelski A, Tepp WH, Kroken AR, Fu Z, Kim JJ, Johnson EA, Barbieri JT. Enhancing the Protective Immune Response against Botulism. Infect Immun. 2013 May 13. PMID:23670557 doi:10.1128/IAI.00382-13

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/4iqp"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of HCRA-W1266A==
 <StructureSection load='4iqp' size='340' side='right' caption='[[4iqp]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4iqp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IQP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IQP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4iqp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_botulinus"_van_ermengem_1896 "bacillus botulinus" van ermengem 1896]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IQP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IQP FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3fuo|3fuo]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">atx, bna, botA, Botulinum neurotoxin type A receptor binding domain ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 Clostridium botulinum])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">atx, bna, botA, Botulinum neurotoxin type A receptor binding domain ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 "Bacillus botulinus" van Ermengem 1896])</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=4iqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iqp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iqp RCSB], [http://www.ebi.ac.uk/pdbsum/4iqp 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=4iqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iqp OCA], [http://pdbe.org/4iqp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iqp RCSB], [http://www.ebi.ac.uk/pdbsum/4iqp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iqp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4iqp" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Botulinum neurotoxin|Botulinum neurotoxin]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Bacillus botulinus van ermengem 1896]]
 [[Category: Bontoxilysin]]
-[[Category: Clostridium botulinum]]
 [[Category: Barbieri, J T]]
 [[Category: Fu, Z]]

4iqp

From Proteopedia

Revision as of 23:34, 5 August 2016

Crystal Structure of HCRA-W1266A

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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