Borden Lacy
Last active: 3/24/2020

Crystal structure of botulinum neurotoxin type A and implications for toxicity.

Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC
Nat Struct Biol. 1998 5 (10): 898-902

PMID: 9783750 · DOI:10.1038/2338

Botulinum neurotoxin type A (BoNT/A) is the potent disease agent in botulism, a potential biological weapon and an effective therapeutic drug for involuntary muscle disorders. The crystal structure of the entire 1,285 amino acid di-chain neurotoxin was determined at 3.3 A resolution. The structure reveals that the translocation domain contains a central pair of alpha-helices 105 A long and a approximately 50 residue loop or belt that wraps around the catalytic domain. This belt partially occludes a large channel leading to a buried, negative active site--a feature that calls for radically different inhibitor design strategies from those currently used. The fold of the translocation domain suggests a mechanism of pore formation different from other toxins. Lastly, the toxin appears as a hybrid of varied structural motifs and suggests a modular assembly of functional subunits to yield pathogenesis.

MeSH Terms (6)

Binding Sites Botulinum Toxins, Type A Catalysis Crystallography, X-Ray Models, Molecular Protein Structure, Secondary

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