title: Botulinum neurotoxins are zinc proteins.
abstract: The available amino acid sequences of 150-kDa botulinum and tetanus neurotoxins show the presence of a closely homologous segment in the middle of the light chain (NH2-terminal 50 kDa), which is the intracellularly active portion of the toxin. This segment contains the zinc binding motif of metalloendopeptidases, HEXXH. Atomic adsorption analysis of botulinum neurotoxins (serotypes A, B, and E) made on the basis of this observation demonstrated the presence of one zinc atom/molecule of 150-kDa neurotoxin. Conditions were found for the removal of the zinc ion with chelating agents and for the restoration of the normal metal content. The conserved segment, which includes the zinc binding motif, was synthesized and shown to bind [65Zn]2+. Chemical modification experiments indicated that two histidines and no cysteines are involved in Zn2+ coordination in agreement with a probable catalytic role for the zinc ion. The present findings suggest the possibility that botulinum neurotoxins are zinc proteases.
authors.affiliation: Centro Consiglio Nazionale delle Ricerche Biomembrane, Università di Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Schiavo
authors.forename: O
authors.initials: O
authors.lastname: Rossetto
authors.forename: A
authors.initials: A
authors.lastname: Santucci
authors.forename: B R
authors.initials: BR
authors.lastname: DasGupta
authors.forename: C
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000595:Amino Acid Sequence; D001905:Botulinum Toxins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D008667:Metalloproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis; D017386:Sequence Homology, Amino Acid; D015032:Zinc / Q000032:analysis* / Q000378:metabolism
chemical_list: D008667:Metalloproteins; D009498:Neurotoxins; D010446:Peptide Fragments; D001905:Botulinum Toxins; D015032:Zinc