ArticleFrontiers in pharmacology2012
Tyrosine phosphorylation of botulinum neurotoxin protease domains.
Article in Frontiers in pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- The Use of Botulinum Toxin in the Management of Headache Disorders.Handbook of experimental pharmacology · 2021Trial
- Unraveling Botulinum Neurotoxin A Light-Chain-Induced Signaling Pathways: A Phosphoproteomic Analysis in a Controlled Cellular Model.International journal of molecular sciences · 2025Article
- Collateral beauty in the damages: an overview of cosmetics and therapeutic applications of microbial proteases.Archives of microbiology · 2023Review
- The mechanisms of action and use of botulinum neurotoxin type A in aesthetics: Key Clinical Postulates II.Journal of cosmetic dermatology · 2020Review
- Article
- Cellular Protection of SNAP-25 against Botulinum Neurotoxin/A: Inhibition of Thioredoxin Reductase through a Suicide Substrate Mechanism.Journal of the American Chemical Society · 2016Article
- SRC family kinase inhibitors antagonize the toxicity of multiple serotypes of botulinum neurotoxin in human embryonic stem cell-derived motor neurons.Neurotoxicity research · 2015Article
- Article
- Cleavage of SNAP25 and its shorter versions by the protease domain of serotype A botulinum neurotoxin.PloS one · 2014Article
- Botulinum neurotoxins A and E undergo retrograde axonal transport in primary motor neurons.PLoS pathogens · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Botulinum neurotoxins are most potent of all toxins. Their N-terminal light chain domain (Lc) translocates into peripheral cholinergic neurons to exert its endoproteolytic action leading to muscle paralysis. Therapeutic development against these toxins is a major challenge due to their in vitro and in vivo structural differences. Although three-dimensional structures and reaction mechanisms are very similar, the seven serotypes designated A through G vastly vary in their intracellular catalytic stability. To investigate if protein phosphorylation could account for this difference, we employed Src-catalyzed tyrosine phosphorylation of the Lc of six serotypes namely LcA, LcB, LcC1, LcD, LcE, and LcG. Very little phosphorylation was observed with LcD and LcE but LcA, LcB, and LcG were maximally phosphorylated by Src. Phosphorylation of LcA, LcB, and LcG did not affect their secondary and tertiary structures and thermostability significantly. Phosphorylation of Y250 and Y251 made LcA resistant to autocatalysis and drastically reduced its k(cat)/K(m) for catalysis. A tyrosine residue present near the essential cysteine at the C-terminal tail of LcA, LcB, and LcG was readily phosphorylated in vitro. Inclusion of a competitive inhibitor protected Y426 of LcA from phosphorylation, shedding light on the role of the C-terminus in the enzyme's substrate or product binding.
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