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Structural characte...
Structural characterisation of the catalytic domain of botulinum neurotoxin X - high activity and unique substrate specificity
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- Masuyer, Geoffrey (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Zhang, Sicai (författare)
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Barkho, Sulyman (författare)
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Shen, Yi (författare)
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- Henriksson, Linda (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Košenina, Sara (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Dong, Min (författare)
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- Stenmark, Pål (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik
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(creator_code:org_t)
- 2018-03-14
- 2018
- Engelska.
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
- Relaterad länk:
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https://doi.org/10.1...
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https://su.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used to treat an increasing number of medical disorders. There are seven well-established serotypes (BoNT/A-G), which all act as zinc-dependent endopeptidases targeting specific members of the SNARE proteins required for synaptic vesicle exocytosis in neurons. A new toxin serotype, BoNT/X, was recently identified. It cleaves not only the canonical targets, vesicle associated membrane proteins (VAMP) 1/2/3 at a unique site, but also has the unique ability to cleave VAMP4/5 and Ykt6. Here we report the 1.35 angstrom X-ray crystal structure of the light chain of BoNT/X (LC/X). LC/X shares the core fold common to all other BoNTs, demonstrating that LC/X is a bona fide member of BoNT-LCs. We found that access to the catalytic pocket of LC/X is more restricted, and the regions lining the catalytic pocket are not conserved compared to other BoNTs. Kinetic studies revealed that LC/X cleaves VAMP1 with a ten times higher efficiency than BoNT/B and the tetanus neurotoxin. The structural information provides a molecular basis to understand the convergence/divergence between BoNT/X and other BoNTs, to develop effective LC inhibitors, and to engineer new scientific tools and therapeutic toxins targeting distinct SNARE proteins in cells.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Nyckelord
- biokemi
- Biochemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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