Crystal structure of botulinum neurotoxin type A and implications for toxicity.
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1,659 citations
Cites background from "Crystal structure of botulinum neur..."
...3 A.(38) The toxin’s light chain is a Zncontaining endopeptidase that blocks acetylcholine-containing vesicles from fusingwiththeterminalmembraneof the motorneuron, resulting in flaccidmuscle paralysis (FIGURE 1)....
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1,196 citations
Cites background from "Crystal structure of botulinum neur..."
...Here we only mention results that are relevant with respect to the recent identification of a sugar-binding subdomain in BoNT/A and TeNT (326, 610)....
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...Two experimental results do not fit in this model: 1) the L chains of TeNT and BoNT/A, /B, and /E penetrate the lipid bilayer in such a way as to be exposed to the fatty acid chains of phospholipids, i.e., they are not shielded from lipids inside the H chain tunnel (420, 421); and 2) values of the order of a few tens of picoSiemens do not account for the dimensions expected for a protein channel that has to accommodate a polypeptide chain with lateral groups of different volume, charge, and hydrophilicity....
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...The HC domains of TeNT and BoNT/A, /B, and /E appear to be sufficient for the internalization process in murine spinal cord neurons (328)....
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...The sugarbinding and protein binding subdomains present in the HC domain of TeNT and BoNT/A (326, 611) and the protection experiments mentioned above support the suggestion that CNT may bind strongly and specifically to the presynaptic membrane because they display multiple interactions with sugar and protein binding sites (413)....
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...Another characteritic of the active site of BoNT/A is that it is 20–24 Å deep in the protein and that it is accessible via an anionic channel, not accessible in the intact molecule because it is shielded by HN and its wrapping belt (326)....
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Cites background from "Crystal structure of botulinum neur..."
...Examination of the three-dimensional structure of BoNT/A shows that when the interchain disulphide bridge that links heavy and light chains is intact, the N-terminal portion of the heavy chain masks the catalytic cleft in the light chain, thereby preventing substrate access [15]....
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...Finally, the tridimensional structure of botulinum neurotoxin type A has now been resolved [15]....
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...Only the tridimensional structure of BoNT/A has been resolved [15]....
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References
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"Crystal structure of botulinum neur..." refers background in this paper
...In fact, the long pair of a-helices with their triple helix bundles at either end bear more resemblance to the coiled coil viral proteins: HIV-1 gp41/GCN4, influenza hemagglutinin, and the MoMuLV TM fragmen...
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