ArticleProceedings of the National Academy of Sciences of the United States of America2016
Human DNMT1 transition state structure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 70 citations in OpenAlex.
- Quantum tunneling in DNA methylation: A computational study using QM/MM and molecular dynamics.Biophysical journal · 2026Article
- Recent Advances in Searching for DNMT Inhibitors and Their Potential Application in Treating Human Diseases.International journal of molecular sciences · 2026Review
- The potential and promise of natural antioxidants as epigenetic modulators in oral squamous cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- Transition State Analysis of SAMHD1 from PrimaryJournal of the American Chemical Society · 2025Article
- Trophic transfer of carbon-14 from algae to zebrafish leads to its blending in biomolecules and the dysregulation of metabolism via isotope effect.National science review · 2025Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- The Role of DNMT Methyltransferases and TET Dioxygenases in the Maintenance of the DNA Methylation Level.Biomolecules · 2024Review
- Cytosine analogues as DNA methyltransferase substrates.Nucleic acids research · 2024Article
- Important role of DNA methylation hints at significant potential in tuberculosis.Archives of microbiology · 2024Review
- Classical swine fever virus non-structural protein 5B hijacks host METTL14-mediated m6A modification to counteract host antiviral immune response.PLoS pathogens · 2024Article
- Habitual Daily Intake of Fried Foods Raises Transgenerational Inheritance Risk of Heart Failure Through NOTCH1-Triggered Apoptosis.Research (Washington, D.C.) · 2024Article
- Ghost authors revealed: The structure and function of human NWiley interdisciplinary reviews. RNA · 2023Review
- Unveiling the methyl transfer mechanisms in the epigenetic machinery DNMT3A-3 L: A comprehensive study integrating assembly dynamics with catalytic reactions.Computational and structural biotechnology journal · 2023Article
- The Interaction between DNMT1 and High-Mannose CD133 Maintains the Slow-Cycling State and Tumorigenic Potential of Glioma Stem Cell.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Synthesis and Characterization of Transition-State Analogue Inhibitors against Human DNA Methyltransferase 1.Journal of medicinal chemistry · 2022Article
- Enzymology of Mammalian DNA Methyltransferases.Advances in experimental medicine and biology · 2022Article
- Acetylated DNMT1 Downregulation and Related Regulatory Factors Influence Metastatic Melanoma Patients Survival.Cancers · 2021Article
- 5-Hydroxymethyl-, 5-Formyl- and 5-Carboxydeoxycytidines as Oxidative Lesions and Epigenetic Marks.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Beta class amino methyltransferases from bacteria to humans: evolution and structural consequences.Nucleic acids research · 2020Review
- Epigenetic dynamics in cancer stem cell dormancy.Cancer metastasis reviews · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Human DNA methyltransferase 1 (DNMT1) maintains the epigenetic state of DNA by replicating CpG methylation signatures from parent to daughter strands, producing heritable methylation patterns through cell divisions. The proposed catalytic mechanism of DNMT1 involves nucleophilic attack of Cys(1226) to cytosine (Cyt) C6, methyl transfer from S-adenosyl-l-methionine (SAM) to Cyt C5, and proton abstraction from C5 to form methylated CpG in DNA. Here, we report the subangstrom geometric and electrostatic structure of the major transition state (TS) of the reaction catalyzed by human DNMT1. Experimental kinetic isotope effects were used to guide quantum mechanical calculations to solve the TS structure. Methyl transfer occurs after Cys(1226) attack to Cyt C6, and the methyl transfer step is chemically rate-limiting for DNMT1. Electrostatic potential maps were compared for the TS and ground states, providing the electronic basis for interactions between the protein and reactants at the TS. Understanding the TS of DNMT1 demonstrates the possibility of using similar analysis to gain subangstrom geometric insight into the complex reactions of epigenetic modifications.
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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.