Journal ArticleDOI
Crystal structure of botulinum neurotoxin type A and implications for toxicity.
TLDR
The crystal structure of the entire 1,285 amino acid di-chain neurotoxin was determined and the toxin appears as a hybrid of varied structural motifs and suggests a modular assembly of functional subunits to yield pathogenesis.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.read more
Citations
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Journal ArticleDOI
Utilizing Ayurvedic literature for the identification of novel phytochemical inhibitors of botulinum neurotoxin A
C Yalamanchili,Vamshi K. Manda,Amar G. Chittiboyina,Rebecca L. Guernieri,William A. Harrell,Robert P. Webb,Leonard A. Smith,Ikhlas A. Khan +7 more
TL;DR: The identification of acoric acid 1, a novel scaffold against BoNT/A, exemplifies the utility of Ayurvedic literature for the discovery of novel drug leads.
Patent
Designer ubiquitin ligases having a non-cleavable SNAP25 domain and E3-ligase domain
George A. Oyler,Yien Che Tsai +1 more
TL;DR: In this paper, a designer or recombinant ubiquitin ligase molecule that includes a toxin binding domain that is specific for a toxin active fragment, wherein the toxin is an enzymatically active fragment of one or more toxins or toxin serotypes, was presented.
Journal ArticleDOI
Presynaptic targeting of botulinum neurotoxin type A requires a tripartite PSG‐Syt1‐SV2 plasma membrane nanocluster for synaptic vesicle entry
Merja Joensuu,Parnayan Syed,Saber H. Saber,Vanessa Lanoue,Tristan P. Wallis,James Rae,Ailisa Blum,Rachel S. Gormal,Christopher Small,Shanley Sanders,Anmin Jiang,Stefan Mahrhold,Nadja Krez,Michael A. Cousin,Ruby Cooper-White,Justin J. Cooper-White,Brett M. Collins,Robert G. Parton,Giuseppe Balistreri,Andreas Rummel,Frederic A. Meunier +20 more
TL;DR: In this article , the authors demonstrate that the targeted endocytosis of botulinum neurotoxin type A into synaptic vesicles (SVs) requires a tripartite surface nanocluster.
Dissertation
Evaluation multidimensionnelle dans les indications et bénéfices des injections de toxine botulique chez l’enfant paralysé cérébral
TL;DR: Pour objectif d’aborder l’evaluation du traitement par TB de maniere multidimensionnelle, nous apportons dans ce travail diverses etudes permettant d”apprehender une approche globale.
References
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Journal ArticleDOI
Atomic structure of the ectodomain from HIV-1 gp41
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Stephen S. Arnon,Robert Schechter,Thomas V. Inglesby,Donald A. Henderson,John G. Bartlett,Michael S. Ascher,Edward M. Eitzen,Anne D. Fine,Jerome Hauer,Marcelle Layton,Scott R. Lillibridge,Michael T. Osterholm,Tara O'Toole,Gerald W. Parker,Trish M. Perl,Philip K. Russell,David L. Swerdlow,Kevin Tonat +17 more