2w2d: Difference between revisions
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<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=2w2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w2d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2w2d RCSB], [http://www.ebi.ac.uk/pdbsum/2w2d 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=2w2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w2d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2w2d RCSB], [http://www.ebi.ac.uk/pdbsum/2w2d PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[[http://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. | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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[[Category: Bontoxilysin]] | [[Category: Bontoxilysin]] | ||
[[Category: Clostridium botulinum]] | [[Category: Clostridium botulinum]] | ||
[[Category: Acharya, K R | [[Category: Acharya, K R]] | ||
[[Category: Chaddock, J A | [[Category: Chaddock, J A]] | ||
[[Category: James, P L | [[Category: James, P L]] | ||
[[Category: Marks, P M.H | [[Category: Marks, P M.H]] | ||
[[Category: Masuyer, G | [[Category: Masuyer, G]] | ||
[[Category: Thiyagarajan, N | [[Category: Thiyagarajan, N]] | ||
[[Category: Bont]] | [[Category: Bont]] | ||
[[Category: Hydrolase]] | [[Category: Hydrolase]] | ||
Revision as of 19:10, 25 December 2014
Crystal Structure of a Catalytically Active, Non-toxic Endopeptidase Derivative of Clostridium botulinum Toxin ACrystal Structure of a Catalytically Active, Non-toxic Endopeptidase Derivative of Clostridium botulinum Toxin A
Structural highlights
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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBotulinum neurotoxins (BoNTs) modulate cholinergic nerve terminals to result in neurotransmitter blockade. BoNTs consists of catalytic (LC), translocation (Hn) and cell-binding domains (Hc). The binding function of the Hc domain is essential for BoNTs to bind the neuronal cell membrane, therefore, removal of the Hc domain results in a product that retains the endopeptidase activity of the LC but is non-toxic. Thus, a molecule consisting of LC and Hn domains of BoNTs, termed LHn, is a suitable molecule for engineering novel therapeutics. The structure of LHA at 2.6 A reported here provides an understanding of the structural implications and challenges of engineering therapeutic molecules that combine functional properties of LHn of BoNTs with specific ligand partners to target different cell types. Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A.,Masuyer G, Thiyagarajan N, James PL, Marks PM, Chaddock JA, Acharya KR Biochem Biophys Res Commun. 2009 Mar 27;381(1):50-3. Epub 2009 Feb 8. PMID:19351593[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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