Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B.
Clostridium botulinum neurotoxins are among the most potent toxins to humans. The crystal structures of intact C. botulinum neurotoxin type B (BoNT/B) and its complex with sialyllactose, determined at 1. 8 and 2.6 A resolution, respectively, provide insight into its catalytic and binding sites. The position of the belt region in BoNT/B is different from that in BoNT/A; this observation presents interesting possibilities for designing specific inhibitors that could be used to block the activity of this neurotoxin. The structures of BoNT/B and its complex with sialyllactose provide a detailed description of the active site and a model for interactions between the toxin and its cell surface receptor. The latter may provide valuable information for recombinant vaccine development.
Swaminathan
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Biology Department, Brookhaven National Laboratory, Upton, New York 11973, USA. swami@bnl.gov
Eswaramoorthy
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D000595:Amino Acid Sequence; D001665:Binding Sites; D001905:Botulinum Toxins / Q000737:chemistry* / Q000378:metabolism*; D019274:Botulinum Toxins, Type A / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D003014:Clostridium botulinum / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005732:Gangliosides / Q000378:metabolism; D007785:Lactose / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism
D005732:Gangliosides; D011956:Receptors, Cell Surface; D012794:Sialic Acids; C096323:rimabotulinumtoxinB; C000020:N-acetylneuraminoyllactose; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; D007785:Lactose