ArticlePLoS pathogens2015
Crystal structures of the carboxyl cGMP binding domain of the Plasmodium falciparum cGMP-dependent protein kinase reveal a novel capping triad crucial for merozoite egress.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Directly adopting inverse biosensors to image live cell enzyme activities in nanodomains.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- An acyclic nucleoside phosphonate effectively blocks the egress of the malaria parasite by inhibiting the synthesis of cyclic GMP.Science advances · 2025Article
- Allosteric modulation of protein kinase A in individuals affected by NLPD-PKA, a neurodegenerative disease in which the PRKAR1B L50R variant is expressed.The FEBS journal · 2025Article
- A divergent cyclic nucleotide binding protein promotes Plasmodium ookinete infection of the mosquito.PLoS pathogens · 2025Article
- Aberrant phase separation of two PKA RIβ neurological disorder mutants leads to mechanistically distinct signaling deficits.Cell reports · 2025Article
- Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.PLoS pathogens · 2024Article
- Malaria parasite egress at a glance.Journal of cell science · 2021Review
- Cyclic nucleotide selectivity of protein kinase G isozymes.Protein science : a publication of the Protein Society · 2021Review
- Keep a lid on it: A troika in kinase allostery.The Journal of biological chemistry · 2020Article
- Mechanism of allosteric inhibition in theThe Journal of biological chemistry · 2020Article
- cGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.Naunyn-Schmiedeberg's archives of pharmacology · 2020Review
- Allosteric inhibition explained through conformational ensembles sampling distinct "mixed" states.Computational and structural biotechnology journal · 2020Review
- Review
- Structures of the cGMP-dependent protein kinase in malaria parasites reveal a unique structural relay mechanism for activation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- FRET-based cyclic GMP biosensors measure low cGMP concentrations in cardiomyocytes and neurons.Communications biology · 2019Article
- Article
- In silico Screening and Evaluation of Plasmodium falciparum Protein Kinase 5 (PK5) Inhibitors.ChemMedChem · 2018Article
- Cyclic nucleotide signalling in malaria parasites.Open biology · 2017Review
- Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation.Structure (London, England : 1993) · 2016Article
- Structural Basis of Cyclic Nucleotide Selectivity in cGMP-dependent Protein Kinase II.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
The Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) is a key regulator across the malaria parasite life cycle. Little is known about PfPKG's activation mechanism. Here we report that the carboxyl cyclic nucleotide binding domain functions as a "gatekeeper" for activation by providing the highest cGMP affinity and selectivity. To understand the mechanism, we have solved its crystal structures with and without cGMP at 2.0 and 1.9 Å, respectively. These structures revealed a PfPKG-specific capping triad that forms upon cGMP binding, and disrupting the triad reduces kinase activity by 90%. Furthermore, mutating these residues in the parasite prevents blood stage merozoite egress, confirming the essential nature of the triad in the parasite. We propose a mechanism of activation where cGMP binding allosterically triggers the conformational change at the αC-helix, which bridges the regulatory and catalytic domains, causing the capping triad to form and stabilize the active conformation.
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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.