Engineered botulinum neurotoxin B with improved binding to human receptors has enhanced efficacy in preclinical models.
Animals
Botulinum Toxins, Type A
/ chemistry
Crystallography, X-Ray
Female
Glycine
/ metabolism
Humans
Induced Pluripotent Stem Cells
/ drug effects
Male
Mice, Inbred C57BL
Mice, Transgenic
Muscle, Skeletal
/ drug effects
Muscle, Smooth
/ drug effects
Mutation
Neurons
/ drug effects
Protein Engineering
Rabbits
Rats, Sprague-Dawley
Recombinant Proteins
/ genetics
Static Electricity
Synaptotagmin II
/ chemistry
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
09
07
2018
accepted:
06
12
2018
entrez:
13
2
2019
pubmed:
13
2
2019
medline:
22
4
2020
Statut:
epublish
Résumé
Although botulinum neurotoxin serotype A (BoNT/A) products are common treatments for various disorders, there is only one commercial BoNT/B product, whose low potency, likely stemming from low affinity toward its human receptor synaptotagmin 2 (hSyt2), has limited its therapeutic usefulness. We express and characterize two full-length recombinant BoNT/B1 proteins containing designed mutations E1191M/S1199Y (rBoNT/B1
Identifiants
pubmed: 30746458
doi: 10.1126/sciadv.aau7196
pii: aau7196
pmc: PMC6357751
doi:
Substances chimiques
Recombinant Proteins
0
SYT2 protein, human
0
Synaptotagmin II
0
rimabotulinumtoxinB
0Y70779M1F
Botulinum Toxins, Type A
EC 3.4.24.69
Glycine
TE7660XO1C
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaau7196Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK034854
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI132387
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS080833
Pays : United States
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