ArticleNucleic acids research2015
Structure of Naegleria Tet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA.
Article in Nucleic acids research, 2015. 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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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
- Article
- Characterization of the enzyme for 5-hydroxymethyluridine production and its role in silencing transposable elements in dinoflagellates.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Temporal epigenome modulation enables efficient bacteriophage engineering and functional analysis of phage DNA modifications.PLoS genetics · 2024Article
- Molecular basis of an atypical dsDNA 5mC/6mA bifunctional dioxygenase CcTet from Coprinopsis cinerea in catalyzing dsDNA 5mC demethylation.Nucleic acids research · 2024Article
- Spectroscopic and in vitro Investigations of FeChembiochem : a European journal of chemical biology · 2022Review
- Recent Advances on DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications.Advances in experimental medicine and biology · 2022Article
- Gene expression and epigenetic responses of the marine Cladoceran,Ecology and evolution · 2021Article
- Phage-encoded ten-eleven translocation dioxygenase (TET) is active in C5-cytosine hypermodification in DNA.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- TET-dioxygenase deficiency in oncogenesis and its targeting for tumor-selective therapeutics.Seminars in hematology · 2021Review
- Enzymatic Hydroxylation and Excision of Extended 5-Methylcytosine Analogues.Journal of molecular biology · 2020Article
- Site- and degree-specific C-H oxidation on 5-methylcytosine homologues for probing active DNA demethylation.Chemical science · 2019Article
- Harnessing natural DNA modifying activities for editing of the genome and epigenome.Current opinion in chemical biology · 2018Review
- TET family dioxygenases and DNA demethylation in stem cells and cancers.Experimental & molecular medicine · 2017Review
- Mutations along a TET2 active site scaffold stall oxidation at 5-hydroxymethylcytosine.Nature chemical biology · 2017Article
- DNA base flipping analytical pipeline.Biology methods & protocols · 2017Article
- Role of Base Excision "Repair" Enzymes in Erasing Epigenetic Marks from DNA.Chemical reviews · 2016Review
- The expanding scope and impact of epigenetic cytosine modifications.Current opinion in chemical biology · 2016Review
- Role of TET enzymes in DNA methylation, development, and cancer.Genes & development · 2016Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The family of ten-eleven translocation (Tet) dioxygenases is widely distributed across the eukaryotic tree of life, from mammals to the amoeboflagellate Naegleria gruberi. Like mammalian Tet proteins, the Naegleria Tet-like protein, NgTet1, acts on 5-methylcytosine (5mC) and generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in three consecutive, Fe(II)- and α-ketoglutarate-dependent oxidation reactions. The two intermediates, 5hmC and 5fC, could be considered either as the reaction product of the previous enzymatic cycle or the substrate for the next cycle. Here we present a new crystal structure of NgTet1 in complex with DNA containing a 5hmC. Along with the previously solved NgTet1-5mC structure, the two complexes offer a detailed picture of the active site at individual stages of the reaction cycle. In the crystal, the hydroxymethyl (OH-CH2-) moiety of 5hmC points to the metal center, representing the reaction product of 5mC hydroxylation. The hydroxyl oxygen atom could be rotated away from the metal center, to a hydrophobic pocket formed by Ala212, Val293 and Phe295. Such rotation turns the hydroxyl oxygen atom away from the product conformation, and exposes the target CH2 towards the metal-ligand water molecule, where a dioxygen O2 molecule would occupy to initiate the next round of reaction by abstracting a hydrogen atom from the substrate. The Ala212-to-Val (A212V) mutant profoundly limits the product to 5hmC, probably because the reduced hydrophobic pocket size restricts the binding of 5hmC as a substrate.
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