Monoclonal Antibodies Targeting the Alpha-Exosite of Botulinum Neurotoxin Serotype/A Inhibit Catalytic Activity

• Published in: PloS one Vol. 10; no. 8; p. e0135306
• Main Authors: Fan, Yongfeng, Geren, Isin N, Dong, Jianbo, Lou, Jianlong, Wen, Weihua, Conrad, Fraser, Smith, Theresa J, Smith, Leonard A, Ho, Mengfei, Pires-Alves, Melissa, Wilson, Brenda A, Marks, James D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.08.2015; Public Library of Science (PLoS)
• Subjects: Acetylcholine; Alanine; Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - metabolism; Antigenic determinants; Antitoxins; Antitoxins - chemistry; Antitoxins - immunology; Antitoxins - metabolism; Biological products; Botulinum toxin type A; Botulinum Toxins, Type A - immunology; Botulism; Catalysis; Catalytic activity; Chains; Cloning; Clostridium botulinum; Epitope Mapping; Epitopes; Female; Flow cytometry; Fluorescence; Food contamination; Genes; Humans; Immunization; Immunoglobulins; Infectious diseases; Intoxication; Libraries; Mice; Molecular chains; Monoclonal antibodies; Neurotoxins; Neurotoxins - immunology; Neurotransmitter release; Paralysis; Protein Structure, Tertiary; Proteins; Scanning mutagenesis; Serogroup; Single-Chain Antibodies - metabolism; SNAP receptors; Toxins; Waterborne diseases; Yeast; Zinc; Zinc endopeptidase; San Francisco California; California; United States > US; Maryland; Illinois

The paralytic disease botulism is caused by botulinum neurotoxins (BoNT), multi-domain proteins containing a zinc endopeptidase that cleaves the cognate SNARE protein, thereby blocking acetylcholine neurotransmitter release. Antitoxins currently used to treat botulism neutralize circulating BoNT but...