ArticleThe Journal of physiology2005
High affinity ATP/ADP analogues as new tools for studying CFTR gating.
Article in The Journal of physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- Altered functional interactions between CFTR disease mutants ΔF508 and G551D and the protein kinase A catalytic subunit.The Journal of physiology · 2026Article
- The structures of protein kinase A in complex with CFTR: Mechanisms of phosphorylation and noncatalytic activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Estimating the true stability of the prehydrolytic outward-facing state in an ABC protein.eLife · 2023Article
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Simple binding of protein kinase A prior to phosphorylation allows CFTR anion channels to be opened by nucleotides.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A Photo-clickable ATP-Mimetic Reveals Nucleotide Interactors in the Membrane Proteome.Cell chemical biology · 2020Article
- Identifying the molecular target sites for CFTR potentiators GLPG1837 and VX-770.The Journal of general physiology · 2019Article
- CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine.Frontiers in pharmacology · 2019Review
- Emerging Therapeutic Approaches for Cystic Fibrosis. From Gene Editing to Personalized Medicine.Frontiers in pharmacology · 2019Review
- Ligand binding to a remote site thermodynamically corrects the F508del mutation in the human cystic fibrosis transmembrane conductance regulator.The Journal of biological chemistry · 2018Article
- Combination potentiator ('co-potentiator') therapy for CF caused by CFTR mutants, including N1303K, that are poorly responsive to single potentiators.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2018Article
- Structural mechanisms of CFTR function and dysfunction.The Journal of general physiology · 2018Review
- A common mechanism for CFTR potentiators.The Journal of general physiology · 2017Article
- CFTR potentiators: from bench to bedside.Current opinion in pharmacology · 2017Review
- On the mechanism of gating defects caused by the R117H mutation in cystic fibrosis transmembrane conductance regulator.The Journal of physiology · 2016Article
- The cystic fibrosis transmembrane conductance regulator is an extracellular chloride sensor.Pflugers Archiv : European journal of physiology · 2015Article
- CFTR interacts with ZO-1 to regulate tight junction assembly and epithelial differentiation through the ZONAB pathway.Journal of cell science · 2014Article
- Conformational changes in the catalytically inactive nucleotide-binding site of CFTR.The Journal of general physiology · 2013Article
- The CFTR ion channel: gating, regulation, and anion permeation.Cold Spring Harbor perspectives in medicine · 2013Article
- Identification of a novel post-hydrolytic state in CFTR gating.The Journal of general physiology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Previous studies using non-hydrolysable ATP analogues and hydrolysis-deficient cystic fibrosis transmembrane conductance regulator (CFTR) mutants have indicated that ATP hydrolysis precedes channel closing. Our recent data suggest that ATP binding is also important in modulating the closing rate. This latter hypothesis predicts that ATP analogues with higher binding affinities should stabilize the open state more than ATP. Here we explore the possibility of using N6-modified ATP/ADP analogues as high-affinity ligands for CFTR gating, since these analogues have been shown to be more potent than native ATP/ADP in other ATP-binding proteins. Among the three N6-modified ATP analogues tested, N6-(2-phenylethyl)-ATP (P-ATP) was the most potent, with a K(1/2) of 1.6 +/- 0.4 microm (>50-fold more potent than ATP). The maximal open probability (P(o)) in the presence of P-ATP was approximately 30% higher than that of ATP, indicating that P-ATP also has a higher efficacy than ATP. Single-channel kinetic analysis showed that as [P-ATP] was increased, the opening rate increased, whereas the closing rate decreased. The fact that these two kinetic parameters have different sensitivities to changes of [P-ATP] suggests an involvement of two different ATP-binding sites, a high-affinity site modulating channel closing and a low affinity site controlling channel opening. The effect of P-ATP on the stability of open states was more evident when ATP hydrolysis was abolished, either by mutating the nucleotide-binding domain 2 (NBD2) Walker B glutamate (i.e. E1371) or by using the non-hydrolysable ATP analogue AMP-PNP. Similar strategies to develop nucleotide analogues with a modified adenine ring could be valuable for future studies of CFTR gating.
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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.