Crystal structure of botulinum neurotoxin type A and implications for toxicity.
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Lacy DB, Tepp W, Cohen AC, DasGupta BR, Stevens RC
Crystal structure of botulinum neurotoxin type A and implications for toxicity.
Nat Struct Biol. 1998 Oct;5(10):898-902.
- PubMed ID
- 9783750 [ View in PubMed]
- 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.