Reference: Lacy DB, et al. (1998) Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat Struct Biol 5(10):898-902

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Abstract


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.

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Journal Article | Research Support, U.S. Gov't, Non-P.H.S.
Authors
Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC
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