6F47

Crystal structure of the catalytic domain of botulinum neurotoxin X

Summary for 6F47

• Entry DOI: 10.2210/pdb6f47/pdb
• Descriptor: Catalytic domain of botulinum neurotoxin X, ZINC ION (3 entities in total)
• Functional Keywords: botulinum neurotoxin, botulinum toxin, zinc endopeptidase, toxin
• Biological source: Clostridium botulinum
• Total number of polymer chains: 1
• Total formula weight: 52179.10

Authors

Masuyer, G.,Henriksson, L.,Kosenina, S.,Zhang, S.,Barkho, S.,Shen, Y.,Dong, M.,Stenmark, P. (deposition date: 2017-11-29, release date: 2018-03-14, Last modification date: 2024-01-17)

Primary citation

Masuyer, G.,Zhang, S.,Barkho, S.,Shen, Y.,Henriksson, L.,Kosenina, S.,Dong, M.,Stenmark, P.
Structural characterisation of the catalytic domain of botulinum neurotoxin X - high activity and unique substrate specificity.
Sci Rep, 8:4518-4518, 2018

PubMed Abstract: 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 Å 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.

PubMed: 29540745
DOI: 10.1038/s41598-018-22842-4

Experimental method

X-RAY DIFFRACTION (1.35 Å)