DNA oxidative demethylase

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DNA oxidative demethylase
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EC no. 1.14.11.33
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DNA oxidative demethylase (EC 1.14.11.33, alkylated DNA repair protein, alpha-ketoglutarate-dependent dioxygenase ABH1, alkB (gene)) is an enzyme with systematic name methyl DNA-base, 2-oxoglutarate:oxygen oxidoreductase (formaldehyde-forming). [1] [2] [3] This enzyme catalyses the following chemical reaction

DNA-base-CH3 + 2-oxoglutarate + O2 DNA-base + formaldehyde + succinate + CO2

DNA oxidative demethylase contains iron; activity is somewhat stimulated by ascorbate.

Related Research Articles

<span class="mw-page-title-main">5-Methylcytosine</span> Chemical compound which is a modified DNA base

5-Methylcytosine is a methylated form of the DNA base cytosine (C) that regulates gene transcription and takes several other biological roles. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes can be altered. 5-Methylcytosine is incorporated in the nucleoside 5-methylcytidine.

Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms.

In biology, reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of histones.

AlkB (Alkylation B) is a protein found in E. coli, induced during an adaptive response and involved in the direct reversal of alkylation damage. AlkB specifically removes alkylation damage to single stranded (SS) DNA caused by SN2 type of chemical agents. It efficiently removes methyl groups from 1-methyl adenines, 3-methyl cytosines in SS DNA. AlkB is an alpha-ketoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins. It oxidatively demethylates the DNA substrate. Demethylation by AlkB is accompanied with release of CO2, succinate, and formaldehyde.

<span class="mw-page-title-main">Gamma-butyrobetaine dioxygenase</span> Protein-coding gene in the species Homo sapiens

Gamma-butyrobetaine dioxygenase is an enzyme that in humans is encoded by the BBOX1 gene. Gamma-butyrobetaine dioxygenase catalyses the formation of L-carnitine from gamma-butyrobetaine, the last step in the L-carnitine biosynthesis pathway. Carnitine is essential for the transport of activated fatty acids across the mitochondrial membrane during mitochondrial beta oxidation. In humans, gamma-butyrobetaine dioxygenase can be found in the kidney (high), liver (moderate), and brain. BBOX1 has recently been identified as a potential cancer gene based on a large-scale microarray data analysis.

<span class="mw-page-title-main">Dioxygenase</span> Class of enzymes

Dioxygenases are oxidoreductase enzymes. Aerobic life, from simple single-celled bacteria species to complex eukaryotic organisms, has evolved to depend on the oxidizing power of dioxygen in various metabolic pathways. From energetic adenosine triphosphate (ATP) generation to xenobiotic degradation, the use of dioxygen as a biological oxidant is widespread and varied in the exact mechanism of its use. Enzymes employ many different schemes to use dioxygen, and this largely depends on the substrate and reaction at hand.

α-Hydroxyglutaric acid Chemical compound

α-Hydroxyglutaric acid is an alpha hydroxy acid form of glutaric acid.

<span class="mw-page-title-main">Tomas Lindahl</span> Swedish-British scientist

Tomas Robert Lindahl FRS FMedSci is a Swedish-British scientist specialising in cancer research. In 2015, he was awarded the Nobel Prize in Chemistry jointly with American chemist Paul L. Modrich and Turkish chemist Aziz Sancar for mechanistic studies of DNA repair.

<span class="mw-page-title-main">DNA demethylation</span> Removal of a methyl group from one or more nucleotides within a DNA molecule.

For molecular biology in mammals, DNA demethylation causes replacement of 5-methylcytosine (5mC) in a DNA sequence by cytosine (C). DNA demethylation can occur by an active process at the site of a 5mC in a DNA sequence or, in replicating cells, by preventing addition of methyl groups to DNA so that the replicated DNA will largely have cytosine in the DNA sequence.

<span class="mw-page-title-main">5-Hydroxymethylcytosine</span> Chemical compound

5-Hydroxymethylcytosine (5hmC) is a DNA pyrimidine nitrogen base derived from cytosine. It is potentially important in epigenetics, because the hydroxymethyl group on the cytosine can possibly switch a gene on and off. It was first seen in bacteriophages in 1952. However, in 2009 it was found to be abundant in human and mouse brains, as well as in embryonic stem cells. In mammals, it can be generated by oxidation of 5-methylcytosine, a reaction mediated by TET enzymes. Its molecular formula is C5H7N3O2.

<span class="mw-page-title-main">Tet methylcytosine dioxygenase 1</span> Mammalian protein found in Homo sapiens

Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is a member of the TET family of enzymes, in humans it is encoded by the TET1 gene. Its function, regulation, and utilizable pathways remain a matter of current research while it seems to be involved in DNA demethylation and therefore gene regulation.

(Histone-H3)-lysine-36 demethylase (EC 1.14.11.27, JHDM1A, JmjC domain-containing histone demethylase 1A, H3-K36-specific demethylase, histone-lysine (H3-K36) demethylase, histone demethylase, protein-6-N,6-N-dimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase) is an enzyme with systematic name protein-N6,N6-dimethyl-L-lysine,2-oxoglutarate:oxygen oxidoreductase. This enzyme catalyses the following chemical reaction

Hypoxia-inducible factor-proline dioxygenase (EC 1.14.11.29, HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating). This enzyme catalyses the following chemical reaction

Thebaine 6-O-demethylase (EC 1.14.11.31, T6ODM) is an enzyme with systematic name thebaine,2-oxoglutarate:oxygen oxidoreductase (6-O-demethylating). This enzyme catalyses the following chemical reaction

Codeine 3-O-demethylase (EC 1.14.11.32, codeine O-demethylase, CODM) is an enzyme with systematic name codeine,2-oxoglutarate:oxygen oxidoreductase (3-O-demethylating). This enzyme catalyses the following chemical reaction

Alpha-ketoglutarate-dependent hydroxylases are a major class of non-heme iron proteins that catalyse a wide range of reactions. These reactions include hydroxylation reactions, demethylations, ring expansions, ring closures, and desaturations. Functionally, the αKG-dependent hydroxylases are comparable to cytochrome P450 enzymes. Both use O2 and reducing equivalents as cosubstrates and both generate water.

Christopher Joseph Schofield is a Professor of Chemistry at the University of Oxford and a Fellow of the Royal Society. Chris Schofield is a professor of organic chemistry at the University of Oxford, Department of Chemistry and a Fellow of Hertford College. Schofield studied functional, structural and mechanistic understanding of enzymes that employ oxygen and 2-oxoglutarate as a co-substrate. His work has opened up new possibilities in antibiotic research, oxygen sensing, and gene regulation.

<span class="mw-page-title-main">AlkB homolog 5, RNA demethylase</span> Protein-coding gene in the species Homo sapiens

RNA demethylase ALKBH5 is a protein that in humans is encoded by the ALKBH5 gene.

<span class="mw-page-title-main">Alkb homolog 1, histone h2a dioxygenase</span> Protein-coding gene in the species Homo sapiens

AlkB homolog 1, histone H2A dioxygenase is a protein that in humans is encoded by the ALKBH1 gene.

<span class="mw-page-title-main">TET enzymes</span> Family of translocation methylcytosine dioxygenases

The TET enzymes are a family of ten-eleven translocation (TET) methylcytosine dioxygenases. They are instrumental in DNA demethylation. 5-Methylcytosine is a methylated form of the DNA base cytosine (C) that often regulates gene transcription and has several other functions in the genome.

References

  1. Falnes PØ, Johansen RF, Seeberg E (September 2002). "AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli". Nature. 419 (6903): 178–82. Bibcode:2002Natur.419..178F. doi:10.1038/nature01048. PMID   12226668.
  2. Yi C, Yang CG, He C (April 2009). "A non-heme iron-mediated chemical demethylation in DNA and RNA". Accounts of Chemical Research. 42 (4): 519–29. doi:10.1021/ar800178j. PMC   2920458 . PMID   19852088.
  3. Yi C, Jia G, Hou G, Dai Q, Zhang W, Zheng G, Jian X, Yang CG, Cui Q, He C (November 2010). "Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase". Nature. 468 (7321): 330–3. Bibcode:2010Natur.468..330Y. doi:10.1038/nature09497. PMC   3058853 . PMID   21068844.