Therapeutic efficacy of new botulinum toxin identified in CCUG 7968 strain

An, Yeongduk; Kim, Young-Je; Kim, Chung-Sei; Yim, Hyeona; Kim, Myungseob; Lee, Eui-Kyung; Oh, Hyeonji; Han, Jun‐Hyeok; Yoo, Eun‐Seon; Kim, Sung-Hyun; Woo, Joong-Seok; Moore, Edward R. B.; Jung, Ji‐Youn; Park, Wooram

doi:10.1007/s00253-021-11640-0

Cited by 3 publications

(1 citation statement)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the four serotypes that infect humans, botulinum neurotoxin A (BoNT/A1) is the most potent followed by serotypes B (BoNT/B), E (BoNT/E) and F (BoNT/F) 11 . Notwithstanding the lethality of this agent, BoNTs are widely exploited in the medical domain to treat a broad range of neurological disorders as well as in the field of cosmetics [12][13][14] BoNTs are composed of two domains comprising a 50 kDa light chain (LC) and a 100 kDa heavy chain (HC). The LC is the catalytic domain of BoNTs.…”

Section: Introductionmentioning

confidence: 99%

Structural basis of botulinum neurotoxin serotype A1 binding to human SV2A or SV2C receptors

Azzaz

Hilaire

Fantini

2022

Preprint

View full text Add to dashboard Cite

Botulinum neurotoxin A1 (BoNT/A1) is the most potent serotype in humans with the highest clinical duration. BoNT/A1 interacts with synaptic vesicle glycoprotein 2 (SV2) and gangliosides to be taken up by neurons. In this study, we present three molecular dynamics simulations in which BoNT/A1 is in complex with singly or doubly glycosylated SV2C or singly glycosylated SV2A, in a ganglioside rich (lipid raft) context. Our computational data suggest that the N-glycan at position 480 (N480g) in the luminal domain of SV2C (LD-SV2C) indirectly enhanced the contacts of the neurotoxin surface with the second N-glycan at position 559 (N559g) by acting as a shield to prevent N559g to interact with residues of LD-SV2C. The N-glycosylation at the position N573 (N573g) in the luminal domain of SV2A has a slightly lower affinity for the surface of BoNT/A1 compared to 559g because of possible intermolecular contacts between N573g and residues of the luminal domain of SV2A (LD-SV2A). In addition to the ganglioside binding site (GBS) conserved across serotypes B, E, F and G, the lipid-raft associated GT1b interacted with a structure we coined the ganglioside binding loop (GBL) which is homologous to the lipid binding loop (LBL) in serotypes B, C, D, D/C and G. Finally, we proposed a global model in which BoNT/A1 interacts with its glycosylated protein receptor, one molecule of GT1b interacting in the GBS and five molecules of GT1b interacting with the GBL and residue Y1133.

show abstract