ArticleJournal of the American Chemical Society2017
Investigation of Trimethyllysine Binding by the HP1 Chromodomain via Unnatural Amino Acid Mutagenesis.
Article in Journal of the American Chemical Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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
22 citing papers in PubMed, 31 citations in OpenAlex.
- Development of m6A Readers for Enhanced Recognition In Vitro via Genetic Code Expansion.ACS chemical biology · 2026Article
- Interplay of Noncovalent Interactions in Phase Separation Mediated by Tyrosine-Rich and Arginine-Rich Polypeptides.Journal of the American Chemical Society · 2026Article
- Influence of the Electrostatic Tuning of Alkyl and Benzyl Groups on Cation-π Interactions in Histone Reader Proteins and β-Hairpin Peptides.Biochemistry · 2026Article
- Negative Cooperativity in the UHRF1 TTD-PHD Dual Domain Masks the Contributions of Cation-π Interactions between Trimethyllysine and the TTD Aromatic Cage.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- WDR5 Binding to Histone Serotonylation Is Driven by an Edge-Face Aromatic Interaction with Unexpected Electrostatic Effects.Journal of the American Chemical Society · 2024Article
- Contribution of Electrostatic CHJournal of the American Chemical Society · 2024Article
- Trimethyllysine Reader Proteins Exhibit Widespread Charge-Agnostic Binding via Different Mechanisms to Cationic and Neutral Ligands.Journal of the American Chemical Society · 2024Article
- Evaluation of acyllysine isostere interactions with the aromatic pocket of the AF9 YEATS domain.Protein science : a publication of the Protein Society · 2023Article
- The Role of Tryptophan in π Interactions in Proteins: An Experimental Approach.Journal of the American Chemical Society · 2022Article
- Comparative Analysis of Sulfonium-π, Ammonium-π, and Sulfur-π Interactions and Relevance to SAM-Dependent Methyltransferases.Journal of the American Chemical Society · 2022Article
- Systematic Variation of Both the Aromatic Cage and Dialkyllysine via GCE-SAR Reveal Mechanistic Insights in CBX5 Reader Protein Binding.Journal of medicinal chemistry · 2022Article
- Methyl-Induced Polarization Destabilizes the Noncovalent Interactions of N-Methylated Lysines.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Contributions of methionine to recognition of trimethyllysine in aromatic cage of PHD domains: implications of polarizability, hydrophobicity, and charge on binding.Chemical science · 2021Article
- Discovery of an H3K36me3-Derived Peptidomimetic Ligand with Enhanced Affinity for Plant Homeodomain Finger Protein 1 (PHF1).Journal of medicinal chemistry · 2021Article
- Trimethyllysine: From Carnitine Biosynthesis to Epigenetics.International journal of molecular sciences · 2020Review
- Engineering a methyllysine reader with photoactive amino acid in mammalian cells.Chemical communications (Cambridge, England) · 2020Article
- More Than π-π-π Stacking: Contribution of Amide-π and CH-π Interactions to Crotonyllysine Binding by the AF9 YEATS Domain.Journal of the American Chemical Society · 2020Article
- Mechanism of biomolecular recognition of trimethyllysine by the fluorinated aromatic cage of KDM5A PHD3 finger.Communications chemistry · 2020Article
- Thermodynamic consequences of Tyr to Trp mutations in the cation-π-mediated binding of trimethyllysine by the HP1 chromodomain.Chemical science · 2020Article
- On the relations of phase separation and Hi-C maps to epigenetics.Royal Society open science · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Trimethyllysine (Kme3) reader proteins are targets for inhibition due to their role in mediating gene expression. Although all such reader proteins bind Kme3 in an aromatic cage, the driving force for binding may differ; some readers exhibit evidence for cation-π interactions whereas others do not. We report a general unnatural amino acid mutagenesis approach to quantify the contribution of individual tyrosines to cation binding using the HP1 chromodomain as a model system. We demonstrate that two tyrosines (Y24 and Y48) bind to a Kme3-histone tail peptide via cation-π interactions, but linear free energy trends suggest they do not contribute equally to binding. X-ray structures and computational analysis suggest that the distance and degree of contact between Tyr residues and Kme3 plays an important role in tuning cation-π-mediated Kme3 recognition. Although cation-π interactions have been studied in a number of proteins, this work is the first to utilize direct binding assays, X-ray crystallography, and modeling, to pinpoint factors that influence the magnitude of the individual cation-π interactions.
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Registered trials
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