3v0b

From Proteopedia

(Difference between revisions)

Current revision

3.9 angstrom crystal structure of BoNT/Ai in complex with NTNHA

Structural highlights

3v0b is a 2 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.9Å
Ligands:	,
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

Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also effective medicines. Accidental BoNT poisoning often occurs through ingestion of Clostridium botulinum-contaminated food. Here, we present the crystal structure of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides large and multivalent binding interfaces to protect BoNT from gastrointestinal degradation. Moreover, the structure highlights key residues in BoNT that regulate complex assembly in a pH-dependent manner. Collectively, our findings define the molecular mechanisms by which NTNHA shields BoNT in the hostile gastrointestinal environment and releases it upon entry into the circulation. These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics.

Botulinum neurotoxin is shielded by NTNHA in an interlocked complex.,Gu S, Rumpel S, Zhou J, Strotmeier J, Bigalke H, Perry K, Shoemaker CB, Rummel A, Jin R Science. 2012 Feb 24;335(6071):977-81. PMID:22363010^[1]

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

References

↑ Gu S, Rumpel S, Zhou J, Strotmeier J, Bigalke H, Perry K, Shoemaker CB, Rummel A, Jin R. Botulinum neurotoxin is shielded by NTNHA in an interlocked complex. Science. 2012 Feb 24;335(6071):977-81. PMID:22363010 doi:10.1126/science.1214270

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/3v0b"

@@ Line 3: / Line 3: @@
 <StructureSection load='3v0b' size='340' side='right'caption='[[3v0b]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3v0b]] is a 2 chain structure with sequence from [https://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=3V0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V0B FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3v0b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_botulinum Clostridium botulinum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V0B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V0B FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.9&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bont/a, boNT/A, bonta ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 "Bacillus botulinus" van Ermengem 1896]), ant, ntnh ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1491 "Bacillus botulinus" van Ermengem 1896])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v0b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v0b OCA], [https://pdbe.org/3v0b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v0b RCSB], [https://www.ebi.ac.uk/pdbsum/3v0b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v0b ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/BXA1_CLOBH 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.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Bacillus botulinus van ermengem 1896]]
+[[Category: Clostridium botulinum]]
 [[Category: Large Structures]]
-[[Category: Bigalke, H]]
+[[Category: Bigalke H]]
-[[Category: Gu, S]]
+[[Category: Gu S]]
-[[Category: Jin, R]]
+[[Category: Jin R]]
-[[Category: Perry, K]]
+[[Category: Perry K]]
-[[Category: Rummel, A]]
+[[Category: Rummel A]]
-[[Category: Rumpel, S]]
+[[Category: Rumpel S]]
-[[Category: Shoemaker, C B]]
+[[Category: Shoemaker CB]]
-[[Category: Strotmeier, J]]
+[[Category: Strotmeier J]]
-[[Category: Zhou, J]]
+[[Category: Zhou J]]
-[[Category: Botulinum neurotoxin]]
-[[Category: Toxin]]
-[[Category: Vhh free inlocked complex]]

3v0b

From Proteopedia

Current revision

3.9 angstrom crystal structure of BoNT/Ai in complex with NTNHA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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