By Karen K. Hill, Theresa J. Smith (auth.), Andreas Rummel, Thomas Binz (eds.)
The super powerful substance botulinum neurotoxin (BoNT) has attracted a lot curiosity in varied fields. initially pointed out as reason for the infrequent yet lethal illness botulism, army and terrorist meant to misuse this refined molecule as organic weapon. This prompted its class as decide on agent classification A by way of the facilities for illnesses keep an eye on and Prevention and the directory within the organic and Toxin guns conference. Later, the civilian use of BoNT as lengthy performing peripheral muscle relaxant has grew to become this molecule into an integral pharmaceutical around the globe with annual sales >$1.5 billion. additionally uncomplicated scientists worth the botulinum neurotoxin as molecular instrument for dissecting mechanisms of exocytosis. This ebook will disguise the latest molecular info of botulinum neurotoxin, its mechanism of motion in addition to its detection and application.
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Extra info for Botulinum Neurotoxins
1977; Sugii et al. 1977). In vitro studies also showed that free BoNTs are much more easily detoxified than those in PTC by pepsin and pancreatin, and by gastric and intestinal juices (Ohishi et al. 1977; Sugii et al. 1977; Sugiyama 1980). To reproduce the physiological conditions faced by BoNT in the GI tract, the response of free BoNT/A and the M-PTC to low pH and digestive proteases was examined. It is found that free BoNT/A was almost completely inactivated by incubation at pH 3 or less, but remained fully active at pH 4–8.
Protonation of these residues has been reported to be involved in low pH-sensing in the pH-gated urea channel, chloride channel, histidine kinases, and viral membrane fusion proteins (Mueller et al. 2008; Perez and Groisman 2007; Stroffekova et al. 1998; Weeks and Sachs 2001). Using structure-based mutagenesis and in vitro binding assays, Glu982 and Asp1037 of BoNT/A were identified as two key residues that mediate the pHdependent binding between BoNT/A and NTNHA-A. A surface electrostatic potential analysis showed that Glu982 and Asp1037 are located in a generally positively charged surface in HC, whereas the opposing NTNHA surface is negatively charged.
Fortunately, the structure of the M-PTC has prompted to focus on HC, which is responsible for most of the intra-complex interactions and maintains the pHsensing feature observed in the full-length BoNT/A. Which residues could serve as pH sensors? 9, respectively. Protonation of these residues has been reported to be involved in low pH-sensing in the pH-gated urea channel, chloride channel, histidine kinases, and viral membrane fusion proteins (Mueller et al. 2008; Perez and Groisman 2007; Stroffekova et al.
Botulinum Neurotoxins by Karen K. Hill, Theresa J. Smith (auth.), Andreas Rummel, Thomas Binz (eds.)