ArticleACS medicinal chemistry letters2013
The C-terminus of Botulinum A Protease Has Profound and Unanticipated Kinetic Consequences Upon the Catalytic Cleft.
Article in ACS medicinal chemistry letters, 2013. 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, 16 citations in OpenAlex.
- Bifunctional Inhibition of Botulinum Neurotoxin A Protease: Unexpected Active Site Inhibition Enhances Covalent Targeting of an Allosteric Site.Journal of medicinal chemistry · 2025Article
- Biologically Active Compounds of Plants: Structure-Related Antioxidant, Microbiological and Cytotoxic Activity of Selected Carboxylic Acids.Materials (Basel, Switzerland) · 2020Review
- Targeting Metalloenzymes for Therapeutic Intervention.Chemical reviews · 2019Review
- A novel role of C-terminus in introducing a functionally flexible structure critical for the biological activity of botulinum neurotoxin.Scientific reports · 2018Article
- Small molecule metalloprotease inhibitor with in vitro, ex vivo and in vivo efficacy against botulinum neurotoxin serotype A.Toxicon : official journal of the International Society on Toxinology · 2017Article
- Newly Designed Quinolinol Inhibitors Mitigate the Effects of Botulinum Neurotoxin A in Enzymatic, Cell-Based, and ex Vivo Assays.Journal of medicinal chemistry · 2017Article
- Probing BoNT/A protease exosites: implications for inhibitor design and light chain longevity.Biochemistry · 2014Article
- Benzoquinones as inhibitors of botulinum neurotoxin serotype A.Bioorganic & medicinal chemistry · 2014Article
- Structural insight into exosite binding and discovery of novel exosite inhibitors of botulinum neurotoxin serotype A through in silico screening.Journal of computer-aided molecular design · 2014Article
- The C terminus of the catalytic domain of type A botulinum neurotoxin may facilitate product release from the active site.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Botulinum neurotoxins (BoNTs) are among the most deadly poisons known though ironically, they also are of great therapeutic utility. A number of research programs have been initiated to discover small molecule inhibitors of BoNTs metalloprotease activity. Many, though not all of these programs have screened against a truncated and more stable form of the enzyme, that possess comparable catalytic properties to the full length enzyme. Interestingly, several classes of inhibitors notably the hydroxamates, display a large shift in potency between the two enzyme forms. In this report we compare the kinetics of active-site, alpha-exosite and beta-exosite inhibitors versus truncated and full length enzyme. Molecular dynamics simulations conducted with the truncated and homology models of the fully length BoNT LC/A indicate the flexibility of the C-terminus of the full length enzyme is responsible for the potency shifts of active-site proximally binding inhibitors while distal binding (alpha-exosite) inhibitors remain equipotent.
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Registered trials
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.