title: Bacterial toxins with intracellular protease activity.
abstract: The recent determination of their primary sequence has lead to the discovery of the metallo-proteolytic activity of the bacterial toxins responsible for tetanus, botulism and anthrax. The protease domain of these toxins enters into the cytosol where it displays a zinc-dependent endopeptidase activity of remarkable specificity. Tetanus neurotoxin and botulinum neurotoxins type B, D, F and G cleave VAMP, an integral protein of the neurotransmitter containing synaptic vesicles. Botulinum neurotoxins type A and E cleave SNAP-25, while the type C neurotoxin cleaves both SNAP-25 and syntaxin, two proteins located on the cytosolic face of the presynaptic membrane. Such specific proteolysis leads to an impaired function of the neuroexocytosis machinery with blockade of neurotransmitter release and consequent paralysis. The lethal factor of Bacillus anthracis is specific for the MAPkinase-kinases which are cleaved within their amino terminus. In this case, however, such specific biochemical lesion could not be correlated with the pathogenesis of anthrax. The recently determined sequence of the vacuolating cytotoxin of Helicobacter pylori contains within its amino terminal domain elements related to serine-proteases, but such an activity as well as its cytosolic target remains to be detected.
authors.affiliation: Department of Biomedical Sciences, University of Padua, Via G. Colombo 3, 35121, Padua, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Rossetto
authors.forename: M
authors.initials: M
authors.lastname: de Bernard
authors.forename: R
authors.initials: R
authors.lastname: Pellizzari
authors.forename: G
authors.initials: G
authors.lastname: Vitale
authors.forename: P
authors.initials: P
authors.lastname: Caccin
authors.forename: G
authors.initials: G
authors.lastname: Schiavo
authors.forename: C
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D001427:Bacterial Toxins; D010450:Endopeptidases