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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Book ChapterDOI
Chapter 5 – Immune Recognition of Botulinum Neurotoxins A and B: Molecular Elucidation of Immune Protection Against the Toxins
M. Zouhair Atassi,K. Roger Aoki +1 more
Covalent unctionalization of gold nanoparticles as electronic bridges and signal amplifiers towards an electrochemical immunosensor for botulinum neurotoxin type A
TL;DR: In this paper, an efficient approach for modification of AuNPs with multicomponents by diazonium salt couplings was introduced, which greatly increased the efficiency for attachment of biomolecules and subsequently increased the sensitivity.
Journal ArticleDOI
Botulinum Toxin Type A and Its Possible Mechanisms on Wound Healing
TL;DR: The responses of Botulinum toxin type-A on wounds healing and preventing pathological scars like HTS and keloids are explored, and the overall effect BTX-A has on wound healing is comprehended.
Dissertation
Tracing the molecular and evolutionary determinants of novel functions in protein families
TL;DR: Virulence and defense proteins have undergone—and will likely continue to generate—evolutionary novelties, so the necessity to look beyond overall sequence comparison, and assess multiple dimensions of functional innovation in proteins is demonstrated.
Journal Article
Integration of single-cell electropermeabilization together with electrochemical measurement of quantal exocytosis on microchips
TL;DR: Using the same electrochemical electrode to electroporate and record quantal release of catecholamines from an individual chromaffin cell allows precise timing of the stimulus, stimulation of a single cell at a time, and can be used to load membrane impermeant substances into a cell.
References
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Journal ArticleDOI
MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures
TL;DR: The MOLSCRIPT program as discussed by the authors produces plots of protein structures using several different kinds of representations, including simple wire models, ball-and-stick models, CPK models and text labels.
Journal ArticleDOI
Improved methods for building protein models in electron density maps and the location of errors in these models.
TL;DR: In this paper, the authors describe strategies and tools that help to alleviate this problem and simplify the model-building process, quantify the goodness of fit of the model on a per-residue basis and locate possible errors in peptide and side-chain conformations.
Journal ArticleDOI
Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons.
TL;DR: It is demonstrated in this work that the surface tension, water‐organic solvent, transfer‐free energies and the thermodynamics of melting of linear alkanes provide fundamental insights into the nonpolar driving forces for protein folding and protein binding reactions.
Journal ArticleDOI
Improved Fourier coefficients for maps using phases from partial structures with errors
TL;DR: In this article, a method is given to estimate the parameter σA in these phase probability expressions from the observed and calculated structure factor amplitudes, from which one can estimate the mean coordinate error for the model, and when there are coordinate errors, a new expression for the non-centric Fourier coefficients is required to suppress this model bias.
Journal ArticleDOI
Atomic structure of the ectodomain from HIV-1 gp41
Winfried Weissenhorn,Andréa Dessen,Stephen C. Harrison,Stephen C. Harrison,John J. Skehel,Don C. Wiley,Don C. Wiley +6 more
TL;DR: X-ray crystallography determines the structure of the protease-resistant part of a gp41 ectodomain solubilized with a trimeric GCN4 coiled coil in place of the amino-terminal fusion peptide, and suggests a common mechanism for initiating fusion.
Related Papers (5)
Botulinum Toxin as a Biological Weapon: Medical and Public Health Management
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