ArticleThe Journal of general physiology2006
A cation-pi interaction between extracellular TEA and an aromatic residue in potassium channels.
Article in The Journal of general physiology, 2006. 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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34 citing papers in PubMed, 62 citations in OpenAlex.
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- Comediation of voltage gating and ion charge in MXene membrane for controllable and selective monovalent cation separation.Science advances · 2024Article
- Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology.Chemical reviews · 2024Review
- Expression and purification of fluorinated proteins from mammalian suspension culture.Methods in enzymology · 2024Article
- Tinker, Tailor, Soldier, Spy: The Diverse Roles That Fluorine Can Play within Amino Acid Side Chains.Molecules (Basel, Switzerland) · 2023Review
- Role of a conserved ion-binding site tyrosine in ion selectivity of the Na+/K+ pump.The Journal of general physiology · 2022Article
- Divergent CleLife · 2020Article
- Alkylphenol inverse agonists of HCN1 gating: H-bond propensity, ring saturation and adduct geometry differentially determine efficacy and potency.Biochemical pharmacology · 2019Article
- The Insensitivity of TASK-3 K₂P Channels to External Tetraethylammonium (TEA) Partially Depends on the Cap Structure.International journal of molecular sciences · 2018Article
- Probing the molecular basis of hERG drug block with unnatural amino acids.Scientific reports · 2018Article
- In vivo incorporation of non-canonical amino acids by using the chemical aminoacylation strategy: a broadly applicable mechanistic tool.Chembiochem : a European journal of chemical biology · 2014Review
- Tethered spectroscopic probes estimate dynamic distances with subnanometer resolution in voltage-dependent potassium channels.Biophysical journal · 2013Article
- Intermediate state trapping of a voltage sensor.The Journal of general physiology · 2012Article
- Interactions of external K+ and internal blockers in a weak inward-rectifier K+ channel.The Journal of general physiology · 2012Article
- Identification of selective inhibitors of the potassium channel Kv1.1-1.2((3)) by high-throughput virtual screening and automated patch clamp.ChemMedChem · 2012Article
- Tuning the tetraethylammonium sensitivity of potassium channel Kcv by subunit combination.The Journal of general physiology · 2012Article
- Contributions of conserved residues at the gating interface of glycine receptors.The Journal of biological chemistry · 2011Article
- Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels.Nature communications · 2011Article
- Allosteric block of KCa2 channels by apamin.The Journal of biological chemistry · 2010Article
- An electrostatic interaction between TEA and an introduced pore aromatic drives spring-in-the-door inactivation in Shaker potassium channels.The Journal of general physiology · 2009Article
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5 authors at 3 institutions in 1 country.
Funding
Abstract
Open-channel blockers such as tetraethylammonium (TEA) have a long history as probes of the permeation pathway of ion channels. High affinity blockade by extracellular TEA requires the presence of an aromatic amino acid at a position that sits at the external entrance of the permeation pathway (residue 449 in the eukaryotic voltage-gated potassium channel Shaker). We investigated whether a cation-pi interaction between TEA and such an aromatic residue contributes to TEA block using the in vivo nonsense suppression method to incorporate a series of increasingly fluorinated Phe side chains at position 449. Fluorination, which is known to decrease the cation-pi binding ability of an aromatic ring, progressively increased the inhibitory constant K(i) for the TEA block of Shaker. A larger increase in K(i) was observed when the benzene ring of Phe449 was substituted by nonaromatic cyclohexane. These results support a strong cation-pi component to the TEA block. The data provide an empirical basis for choosing between Shaker models that are based on two classes of reported crystal structures for the bacterial channel KcsA, showing residue Tyr82 in orientations either compatible or incompatible with a cation-pi mechanism. We propose that the aromatic residue at this position in Shaker is favorably oriented for a cation-pi interaction with the permeation pathway. This choice is supported by high level ab initio calculations of the predicted effects of Phe modifications on TEA binding energy.
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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.