ArticleNucleic acids research2012
Engineering the DNA cytosine-5 methyltransferase reaction for sequence-specific labeling of DNA.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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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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.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- Live-cell DNMT3A "catalysome" mapping using engineered methyl-transfer pathways.Nucleic acids research · 2026Article
- Mapping Protein Occupancy on DNA with an Unnatural Cytosine Modification.ACS chemical biology · 2026Article
- Dual Stabilization ofJACS Au · 2026Article
- Chemical Expansion of the Methyltransferase Reaction: Tools for DNA Labeling and Epigenome Analysis.Accounts of chemical research · 2023Article
- Enhanced nucleosome assembly at CpG sites containing an extended 5-methylcytosine analogue.Nucleic acids research · 2022Article
- Selective chemical tracking of Dnmt1 catalytic activity in live cells.Molecular cell · 2022Article
- DNA Labeling Using DNA Methyltransferases.Advances in experimental medicine and biology · 2022Article
- Analogs ofMolecular biology · 2022Article
- Discovery of an Unnatural DNA Modification Derived from a Natural Secondary Metabolite.Cell chemical biology · 2021Article
- Article
- Enzymatic Hydroxylation and Excision of Extended 5-Methylcytosine Analogues.Journal of molecular biology · 2020Article
- Methionine Adenosyltransferase Engineering to Enable Bioorthogonal Platforms for AdoMet-Utilizing Enzymes.ACS chemical biology · 2020Article
- Repurposing enzymatic transferase reactions for targeted labeling and analysis of DNA and RNA.Current opinion in biotechnology · 2019Review
- The Bump-and-Hole Tactic: Expanding the Scope of Chemical Genetics.Cell chemical biology · 2018Review
- A general strategy for direct, enzyme-catalyzed conjugation of functional compounds to DNA.Nucleic acids research · 2018Article
- Epigenetic drug discovery: a success story for cofactor interference.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Methyltransferase-Directed Labeling of Biomolecules and its Applications.Angewandte Chemie (International ed. in English) · 2017Review
- SAM/SAH Analogs as Versatile Tools for SAM-Dependent Methyltransferases.ACS chemical biology · 2016Review
- Synthesis of S-Adenosyl-L-Methionine Analogs with Extended Transferable Groups for Methyltransferase-Directed Labeling of DNA and RNA.Current protocols in nucleic acid chemistry · 2016Article
- DNA Labeling Using DNA Methyltransferases.Advances in experimental medicine and biology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
DNA methyltransferases catalyse the transfer of a methyl group from the ubiquitous cofactor S-adenosyl-L-methionine (AdoMet) onto specific target sites on DNA and play important roles in organisms from bacteria to humans. AdoMet analogs with extended propargylic side chains have been chemically produced for methyltransferase-directed transfer of activated groups (mTAG) onto DNA, although the efficiency of reactions with synthetic analogs remained low. We performed steric engineering of the cofactor pocket in a model DNA cytosine-5 methyltransferase (C5-MTase), M.HhaI, by systematic replacement of three non-essential positions, located in two conserved sequence motifs and in a variable region, with smaller residues. We found that double and triple replacements lead to a substantial improvement of the transalkylation activity, which manifests itself in a mild increase of cofactor binding affinity and a larger increase of the rate of alkyl transfer. These effects are accompanied with reduction of both the stability of the product DNA-M.HhaI-AdoHcy complex and the rate of methylation, permitting competitive mTAG labeling in the presence of AdoMet. Analogous replacements of two conserved residues in M.HpaII and M2.Eco31I also resulted in improved transalkylation activity attesting a general applicability of the homology-guided engineering to the C5-MTase family and expanding the repertoire of sequence-specific tools for covalent in vitro and ex vivo labeling of DNA.
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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.