2XHL

Structure of a functional derivative of Clostridium botulinum neurotoxin type B

Summary for 2XHL

• Entry DOI: 10.2210/pdb2xhl/pdb
• Related: 1EPW 1F31 1F82 1G9A 1G9B 1G9C 1G9D 1I1E 1S0B 1S0C 1S0D 1S0E 1S0F 1S0G 1Z0H 2ETF
• Descriptor: BOTULINUM NEUROTOXIN B LIGHT CHAIN, BOTULINUM NEUROTOXIN B HEAVY CHAIN, ZINC ION, ... (4 entities in total)
• Functional Keywords: hydrolase, metalloprotease, membrane domain, endopeptidase, zinc protease, botulism, toxin
• Biological source: CLOSTRIDIUM BOTULINUM; More
• Cellular location: Botulinum neurotoxin B light chain: Secreted. Botulinum neurotoxin B heavy chain: Secreted: P10844 P10844
• Total number of polymer chains: 2
• Total formula weight: 102116.11

Authors

Masuyer, G.,Beard, M.,Cadd, V.A.,Chaddock, J.A.,Acharya, K.R. (deposition date: 2010-06-18, release date: 2010-12-01, Last modification date: 2024-10-23)

Primary citation

Masuyer, G.,Beard, M.,Cadd, V.A.,Chaddock, J.A.,Acharya, K.R.
Structure and Activity of a Functional Derivative of Clostridium Botulinum Neurotoxin B.
J.Struct.Biol., 174:52-, 2011

PubMed Abstract: Botulinum neurotoxins (BoNTs) cause flaccid paralysis by inhibiting neurotransmission at cholinergic nerve terminals. BoNTs consist of three essential domains for toxicity: the cell binding domain (Hc), the translocation domain (Hn) and the catalytic domain (LC). A functional derivative (LHn) of the parent neurotoxin B composed of Hn and LC domains was recombinantly produced and characterised. LHn/B crystallographic structure at 2.8Å resolution is reported. The catalytic activity of LHn/B towards recombinant human VAMP was analysed by substrate cleavage assay and showed a higher specificity for VAMP-1, -2 compared to VAMP-3. LHn/B also showed measurable activity in living spinal cord neurons. Despite lacking the Hc (cell-targeting) domain, LHn/B retained the capacity to internalize and cleave intracellular VAMP-1 and -2 when added to the cells at high concentration. These activities of the LHn/B fragment demonstrate the utility of engineered botulinum neurotoxin fragments as analytical tools to study the mechanisms of action of BoNT neurotoxins and of SNARE proteins.

PubMed: 21078393
DOI: 10.1016/J.JSB.2010.11.010

Experimental method

X-RAY DIFFRACTION (2.8 Å)