title: The complete sequence of botulinum neurotoxin type A and comparison with other clostridial neurotoxins.
abstract: The seven serologically different botulinum neurotoxins are highly potent protein toxins that inhibit neurotransmitter release from peripheral cholinergic synapses. The activated toxins consist of the toxifying A-subunits (Mr approximately 50,000) linked by a disulfide bond to the receptor-binding BC-subunits (Mr approximately 100,000). We have established the complete sequence of botulinum neurotoxin type A (BoNT/A; 1,296 amino acid residues, Mr = 149,425) and a partial sequence of botulinum neurotoxin type E (273 amino acid residues) as deduced from the corresponding nucleotide sequences of the chromosomally located structural genes. The promoter of the BoNT/A gene is inactive in Escherichia coli. Primer extension experiments indicated that initiation of transcription of the BoNT/A gene occurred 118 nucleotides upstream from the ATG codon. A comparison of the protein sequence revealed an overall identity of 33.8% to that of tetanus toxin. No significant similarity to other known proteins including ADP-ribosylating toxins could be detected. Three of the six histidine residues of the A-subunit of BoNT/A were found in the peptide sequence H223ELIHXXH230 within a domain of predicted alpha-helical secondary structure. This motif is also found in similar positions of the A-subunits of tetanus toxin and BoNT/E.
authors.affiliation: Institut für Medizinische Virologie der Justus-Liebig-Universität, Giessen, Federal Republic of Germany.
authors.forename: T
authors.initials: T
authors.lastname: Binz
authors.forename: H
authors.initials: H
authors.lastname: Kurazono
authors.forename: M
authors.initials: M
authors.lastname: Wille
authors.forename: J
authors.initials: J
authors.lastname: Frevert
authors.forename: K
authors.initials: K
authors.lastname: Wernars
authors.forename: H
authors.initials: H
authors.lastname: Niemann
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001905:Botulinum Toxins / Q000235:genetics; D003014:Clostridium botulinum / Q000235:genetics; D003062:Codon; D004262:DNA Restriction Enzymes; D004269:DNA, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D010446:Peptide Fragments; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D013744:Tetanus Toxin / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D003062:Codon; D004269:DNA, Bacterial; D015345:Oligonucleotide Probes; D010446:Peptide Fragments; D013744:Tetanus Toxin; D004262:DNA Restriction Enzymes; D001905:Botulinum Toxins