Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

6G5F

Crystal structure of an engineered Botulinum Neurotoxin type B mutant E1191M/S1199Y in complex with human synaptotagmin 1

Summary for 6G5F
Entry DOI10.2210/pdb6g5f/pdb
DescriptorBotulinum neurotoxin type B, Synaptotagmin-1, GLYCEROL, ... (5 entities in total)
Functional Keywordsbotulinum toxin, neurotoxin, protein engineering, receptor binding, toxin
Biological sourceClostridium botulinum
More
Total number of polymer chains3
Total formula weight304983.75
Authors
Primary citationElliott, M.,Favre-Guilmard, C.,Liu, S.M.,Maignel, J.,Masuyer, G.,Beard, M.,Boone, C.,Carre, D.,Kalinichev, M.,Lezmi, S.,Mir, I.,Nicoleau, C.,Palan, S.,Perier, C.,Raban, E.,Zhang, S.,Dong, M.,Stenmark, P.,Krupp, J.
Engineered botulinum neurotoxin B with improved binding to human receptors has enhanced efficacy in preclinical models.
Sci Adv, 5:eaau7196-eaau7196, 2019
Cited by
PubMed Abstract: 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) and E1191Q/S1199W (rBoNT/B1) that enhance binding to hSyt2. In preclinical models including human-induced pluripotent stem cell neurons and a humanized transgenic mouse, this increased hSyt2 affinity results in high potency, comparable to that of BoNT/A. Last, we solve the cocrystal structure of rBoNT/B1 in complex with peptides of hSyt2 and its homolog hSyt1. We demonstrate that neuronal surface receptor binding limits the clinical efficacy of unmodified BoNT/B and that modified BoNT/B proteins have promising clinical potential.
PubMed: 30746458
DOI: 10.1126/sciadv.aau7196
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.5 Å)
Structure validation

238582

PDB entries from 2025-07-09

PDB statisticsPDBj update infoContact PDBjnumon