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PDBsum entry 1s0c
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Toxin, hydrolase
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PDB id
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1s0c
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Role of metals in the biological activity of clostridium botulinum neurotoxins.
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Authors
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S.Eswaramoorthy,
D.Kumaran,
J.Keller,
S.Swaminathan.
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Ref.
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Biochemistry, 2004,
43,
2209-2216.
[DOI no: ]
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PubMed id
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Abstract
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Clostridium botulinum neurotoxins are the most potent toxins to humans and cause
paralysis by blocking neurotransmitter release at the presynaptic nerve
terminals. The toxicity involves four steps, viz., binding to neuronal cells,
internalization, translocation, and catalytic activity. While the catalytic
activity is a zinc endopeptidase activity on the SNARE complex proteins, the
translocation is believed to be a pH-dependent process allowing the
translocation domain to change its conformation to penetrate the endosomal
membrane. Here, we report the crystal structures of botulinum neurotoxin type B
at various pHs and of an apo form of the neurotoxin, and discuss the role of
metal ions and the effect of pH variation in the biological activity. Except for
the perturbation of a few side chains, the conformation of the catalytic domain
is unchanged in the zinc-depleted apotoxin, suggesting that zinc's role is
catalytic. We have also identified two calcium ions in the molecule and present
biochemical evidence to show that they play a role in the translocation of the
light chain through the membrane.
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