ArticleProceedings of the National Academy of Sciences of the United States of America2010
Use of allostery to identify inhibitors of calmodulin-induced activation of Bacillus anthracis edema factor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 68 citations in OpenAlex.
- A systematic evaluation of protein allosteric site prediction tools with independent datasets.Journal of computer-aided molecular design · 2026Article
- Targeting virulence to disarm the pathogen: Enzyme-activated-substrate inhibition of Anthrax edema factor.Bioorganic & medicinal chemistry letters · 2025Article
- MEF-AlloSite: an accurate and robust Multimodel Ensemble Feature selection for the Allosteric Site identification model.Journal of cheminformatics · 2024Article
- PASSerRank: Prediction of allosteric sites with learning to rank.Journal of computational chemistry · 2023Article
- Functional and structural insights into the multi-step activation and catalytic mechanism of bacterial ExoY nucleotidyl cyclase toxins bound to actin-profilin.PLoS pathogens · 2023Article
- PASSer: fast and accurate prediction of protein allosteric sites.Nucleic acids research · 2023Article
- Antihyperglycemic and anti-type 2 diabetic activity of marine hydroquinone isolated from brown algae (Journal of traditional and complementary medicine · 2023Article
- Article
- A Robust and Sensitive Spectrophotometric Assay for the Enzymatic Activity of Bacterial Adenylate Cyclase Toxins.Toxins · 2022Article
- Bacterial Nucleotidyl Cyclases Activated by Calmodulin or Actin in Host Cells: Enzyme Specificities and Cytotoxicity Mechanisms Identified to Date.International journal of molecular sciences · 2022Review
- PASSer2.0: Accurate Prediction of Protein Allosteric Sites Through Automated Machine Learning.Frontiers in molecular biosciences · 2022Article
- PASSer: Prediction of Allosteric Sites Server.Machine learning: science and technology · 2021Article
- Inhibitory properties of saponin fromRSC advances · 2021Article
- AnalyzingFrontiers in molecular biosciences · 2020Article
- Review
- Large-Scale Conformational Changes and Protein Function: Breaking theFrontiers in molecular biosciences · 2019Review
- Designed mono- and di-covalent inhibitors trap modeled functional motions for Trypanosoma cruzi proline racemase in crystallography.PLoS neglected tropical diseases · 2018Article
- Small molecule inhibitors of anthrax edema factor.Bioorganic & medicinal chemistry letters · 2018Article
- Molecular Modeling of the Catalytic Domain of CyaA Deepened the Knowledge of Its Functional Dynamics.Toxins · 2017Review
- JET2 Viewer: a database of predicted multiple, possibly overlapping, protein-protein interaction sites for PDB structures.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Allostery plays a key role in the regulation of the activity and function of many biomolecules. And although many ligands act through allostery, no systematic use is made of it in drug design strategies. Here we describe a procedure for identifying the regions of a protein that can be used to control its activity through allostery. This procedure is based on the construction of a plausible conformational path, which describes protein transition between known active and inactive conformations. The path is calculated by using a framework approach that steers and markedly improves the conjugate peak refinement method. The evolution of conformations along this path was used to identify a putative allosteric site that could regulate activation of Bacillus anthracis adenylyl cyclase toxin (EF) by calmodulin. Conformations of the allosteric site at different steps along the path from the inactive (free) to the active (bound to calmodulin) forms of EF were used to perform virtual screenings and propose candidate EF inhibitors. Several candidates then proved to inhibit calmodulin-induced activation in an in vitro assay. The most potent compound fully inhibited EF at a concentration of 10 microM. The compounds also inhibited the related adenylyl cyclase toxin from Bordetella pertussis (CyaA). The specific homology between the putative allosteric sites in both toxins supports that these pockets are the actual binding sites of the selected inhibitors.
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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.