Evidence map›Paper›PMID 29540745›Full record

ArticleScientific reports2018

Structural characterisation of the catalytic domain of botulinum neurotoxin X - high activity and unique substrate specificity.

Geoffrey Masuyer, Sicai Zhang, Sulyman Barkho, Yi Shen, Linda Henriksson, Sara Košenina, Min Dong, Pål Stenmark

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Review
  3. Investigating the dual nature ofLe infezioni in medicina · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. XeominToxins · 2023
    Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Comparative Genomics ofMicroorganisms · 2022
    Article
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Geoffrey MasuyerDepartment of Biochemistry and Biophysics, Stockholm University, SE-106 91, Stockholm, Sweden.ORCID 0000-0002-9527-2310
Sicai ZhangDepartment of Urology, Boston Children's Hospital, Department of Microbiology and Immunobiology and Department of Surgery, Harvard Medical School, Boston, MA, 02115, USA.
Sulyman BarkhoDepartment of Urology, Boston Children's Hospital, Department of Microbiology and Immunobiology and Department of Surgery, Harvard Medical School, Boston, MA, 02115, USA.
Yi ShenDepartment of Urology, Boston Children's Hospital, Department of Microbiology and Immunobiology and Department of Surgery, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0000-0003-4117-0279
Linda HenrikssonDepartment of Biochemistry and Biophysics, Stockholm University, SE-106 91, Stockholm, Sweden.
Sara KošeninaDepartment of Biochemistry and Biophysics, Stockholm University, SE-106 91, Stockholm, Sweden.
Min DongDepartment of Urology, Boston Children's Hospital, Department of Microbiology and Immunobiology and Department of Surgery, Harvard Medical School, Boston, MA, 02115, USA. min.dong@childrens.harvard.edu.
Pål StenmarkDepartment of Biochemistry and Biophysics, Stockholm University, SE-106 91, Stockholm, Sweden. stenmark@dbb.su.se.
Boston Children's Hospital · USStockholm University · SE

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAYNE I LENCER · 1986 to 2026
$32.4M
SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2M
Long-term effects of botulinum neurotoxins on neuronal viabilityR01NS080833 · NINDS · HARVARD MEDICAL SCHOOL · PI Min Dong · 2013 to 2026
$6.8M
Molecular basis of action and pathogenesis of Clostridium difficile toxin BR01AI132387 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI DONG, MIN · 2017 to 2021
$3.5M
NIAID NIH HHS R01 AI132387NICHD NIH HHS P30 HD018655NIDDK NIH HHS P30 DK034854NINDS NIH HHS R01 NS080833
6 · The paper itself

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.

Indexed as

Catalytic DomainBinding SitesBotulinum Toxins, Type AClostridium botulinumEnzyme ActivationModels, MolecularProtein BindingProtein ConformationStructure-Activity RelationshipSubstrate SpecificityBotulinum Toxins, Type A

Identifiers

PMID29540745
PMCPMC5851995
OpenAlexW2793367962

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.