ArticleProceedings of the National Academy of Sciences of the United States of America2015
Allosteric activation of apicomplexan calcium-dependent protein kinases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 66 citations in OpenAlex.
- Camelid Single-Domain Antibodies as Tools for Novel Target Identification in Kinetoplastid Research.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Growth inhibition of Saccharomyces cerevisiae by SUMO-specific nanobodies.Scientific reports · 2025Article
- Pyridopyrimidinones as a new chemotype of calcium dependent protein kinase 1 (CDPK1) inhibitors for Cryptosporidium.Molecular and biochemical parasitology · 2024Article
- OsCPK12 phosphorylates OsCATA and OsCATC to regulate HPlant communications · 2024Article
- Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis ineLife · 2023Article
- Arabidopsis PLANT U-BOX44 down-regulates osmotic stress signaling by mediating Ca2+-DEPENDENT PROTEIN KINASE4 degradation.The Plant cell · 2023Article
- Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis inbioRxiv : the preprint server for biology · 2023Article
- Proteomic Profiling of Extracellular Matrix Components from Patient Metastases Identifies Consistently Elevated Proteins for Developing Nanobodies That Target Primary Tumors and Metastases.Cancer research · 2023Article
- Temporal and thermal profiling of theeLife · 2022Article
- Multivariate mining of an alpaca immune repertoire identifies potent cross-neutralizing SARS-CoV-2 nanobodies.Science advances · 2022Article
- Phosphorylation-dependent subfunctionalization of the calcium-dependent protein kinase CPK28.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A nanobody suite for yeast scaffold nucleoporins provides details of the nuclear pore complex structure.Nature communications · 2020Article
- Yeast Nup84-Nup133 complex structure details flexibility and reveals conservation of the membrane anchoring ALPS motif.Nature communications · 2020Article
- Exploring cellular biochemistry with nanobodies.The Journal of biological chemistry · 2020Review
- Allosteric inhibition of LRRK2, where are we now.Biochemical Society transactions · 2020Review
- Identifying the Target of an Antiparasitic Compound inACS chemical biology · 2020Article
- Novel Lentivirus-Based Method for Rapid Selection of Inhibitory Nanobody against PRRSV.Viruses · 2020Article
- Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Calcium signaling and the lytic cycle of the Apicomplexan parasite Toxoplasma gondii.Biochimica et biophysica acta. Molecular cell research · 2018Review
- Toxoplasma Calcium-Dependent Protein Kinase 1 Inhibitors: Probing Activity and Resistance Using Cellular Thermal Shift Assays.Antimicrobial agents and chemotherapy · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Calcium-dependent protein kinases (CDPKs) comprise the major group of Ca2+-regulated kinases in plants and protists. It has long been assumed that CDPKs are activated, like other Ca2+-regulated kinases, by derepression of the kinase domain (KD). However, we found that removal of the autoinhibitory domain from Toxoplasma gondii CDPK1 is not sufficient for kinase activation. From a library of heavy chain-only antibody fragments (VHHs), we isolated an antibody (1B7) that binds TgCDPK1 in a conformation-dependent manner and potently inhibits it. We uncovered the molecular basis for this inhibition by solving the crystal structure of the complex and simulating, through molecular dynamics, the effects of 1B7-kinase interactions. In contrast to other Ca2+-regulated kinases, the regulatory domain of TgCDPK1 plays a dual role, inhibiting or activating the kinase in response to changes in Ca2+ concentrations. We propose that the regulatory domain of TgCDPK1 acts as a molecular splint to stabilize the otherwise inactive KD. This dependence on allosteric stabilization reveals a novel susceptibility in this important class of parasite enzymes.
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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.