ArticleThe Journal of biological chemistry2015
Alanine scan of α-conotoxin RegIIA reveals a selective α3β4 nicotinic acetylcholine receptor antagonist.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed.
- The Potential and Prospects of Marine Drugs in Intervening Nerve-Tumor Crosstalk.Marine drugs · 2026Review
- Review
- Redox-Active Conopeptide Li520 Has Evolved to Catalyze Oxidative Folding of Conotoxins.ACS omega · 2024Article
- Single Amino Acid Substitution in Loop1 Switches the Selectivity of α-Conotoxin RegIIA towards the α7 Nicotinic Acetylcholine Receptor.Marine drugs · 2024Article
- Loop2 Size Modification Reveals Significant Impacts on the Potency of α-Conotoxin TxID.Marine drugs · 2023Article
- What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders.Journal of medicinal chemistry · 2023Review
- Cone snail species off the Brazilian coast and their venoms: a review and update.The journal of venomous animals and toxins including tropical diseases · 2023Review
- Review
- Single-Disulfide Conopeptide Czon1107, an Allosteric Antagonist of the Human α3β4 Nicotinic Acetylcholine Receptor.Marine drugs · 2022Article
- A Novel α4/7-Conotoxin QuIA Selectively Inhibits α3β2 and α6/α3β4 Nicotinic Acetylcholine Receptor Subtypes with High Efficacy.Marine drugs · 2022Article
- Mechanism of interactions between α-conotoxin RegIIA and carbohydrates at the human α3β4 nicotinic acetylcholine receptor.Marine life science & technology · 2022Article
- Marine Origin Ligands of Nicotinic Receptors: Low Molecular Compounds, Peptides and Proteins for Fundamental Research and Practical Applications.Biomolecules · 2022Review
- From Crystal Structures of RgIA4 in Complex withMarine drugs · 2021Article
- Characterization of an α 4/7-Conotoxin LvIF fromMarine drugs · 2021Article
- Venom-Derived Neurotoxins Targeting Nicotinic Acetylcholine Receptors.Molecules (Basel, Switzerland) · 2021Review
- α-Conotoxin VnIB from Conus ventricosus is a potent and selective antagonist of α6β4* nicotinic acetylcholine receptors.Neuropharmacology · 2019Article
- DSPE-PEG Modification of α-Conotoxin TxID.Marine drugs · 2019Article
- d-Amino Acid Substitution of α-Conotoxin RgIA Identifies its Critical Residues and Improves the Enzymatic Stability.Marine drugs · 2019Article
- Effect of Methionine Oxidation and Substitution of α-Conotoxin TxID on α3β4 Nicotinic Acetylcholine Receptor.Marine drugs · 2018Article
- Neuronal Nicotinic Acetylcholine Receptor Modulators from Cone Snails.Marine drugs · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the α3β4 nicotinic acetylcholine receptor (nAChR) subtype has recently been implicated in the pathophysiology of various conditions, including development and progression of lung cancer and in nicotine addiction. As selective α3β4 nAChR antagonists, α-conotoxins are valuable tools to evaluate the functional roles of this receptor subtype. We previously reported the discovery of a new α4/7-conotoxin, RegIIA. RegIIA was isolated from Conus regius and inhibits acetylcholine (ACh)-evoked currents mediated by α3β4, α3β2, and α7 nAChR subtypes. The current study used alanine scanning mutagenesis to understand the selectivity profile of RegIIA at the α3β4 nAChR subtype. [N11A] and [N12A] RegIIA analogs exhibited 3-fold more selectivity for the α3β4 than the α3β2 nAChR subtype. We also report synthesis of [N11A,N12A]RegIIA, a selective α3β4 nAChR antagonist (IC50 of 370 nM) that could potentially be used in the treatment of lung cancer and nicotine addiction. Molecular dynamics simulations of RegIIA and [N11A,N12A]RegIIA bound to α3β4 and α3β2 suggest that destabilization of toxin contacts with residues at the principal and complementary faces of α3β2 (α3-Tyr(92), Ser(149), Tyr(189), Cys(192), and Tyr(196); β2-Trp(57), Arg(81), and Phe(119)) may form the molecular basis for the selectivity shift.
Indexed as
Identifiers
What OpenQuestion holds
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.