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Goedecke, Karsten; Pignot, Marc; Goody, Roger S.; Scheidig, Axel J.; Weinhold, Elmar G.

doi:10.1038/84104

Cited by 219 publications

(186 citation statements)

References 27 publications

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“…These MTases are characterized by complete or partial degeneration into coils of the helices before and after strand‐3 18, 79. They also display a helix N‐terminal to the core MTase domain with a conserved residue that helps position the asparagine in the strand‐4‐associated motif in the active site (Fig.…”

Section: Anatomy Of N6a‐mtases‐mtase Domainsmentioning

confidence: 99%

“…3). They are fused to the DNA‐binding MTase‐S domain, which contains a RAGNYA fold, seen in diverse nucleic‐acid‐binding contexts where it recognizes specific nucleotide sequences 79, 86, 87. Clade 5 MTases in the rhizarian Reticulomyxa are found in up to five copies, and at least one is fused to an N‐terminal restriction endonuclease domain, thereby retaining the ancestral Type I R‐M system architecture (Figs.…”

Section: Anatomy Of N6a‐mtases‐mtase Domainsmentioning

confidence: 99%

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Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

2015

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While N6‐methyladenosine (m6A) is a well‐known epigenetic modification in bacterial DNA, it remained largely unstudied in eukaryotes. Recent studies have brought to fore its potential epigenetic role across diverse eukaryotes with biological consequences, which are distinct and possibly even opposite to the well‐studied 5‐methylcytosine mark. Adenine methyltransferases appear to have been independently acquired by eukaryotes on at least 13 occasions from prokaryotic restriction‐modification and counter‐restriction systems. On at least four to five instances, these methyltransferases were recruited as RNA methylases. Thus, m6A marks in eukaryotic DNA and RNA might be more widespread and diversified than previously believed. Several m6A‐binding protein domains from prokaryotes were also acquired by eukaryotes, facilitating prediction of potential readers for these marks. Further, multiple lineages of the AlkB family of dioxygenases have been recruited as m6A demethylases. Although members of the TET/JBP family of dioxygenases have also been suggested to be m6A demethylases, this proposal needs more careful evaluation.Also watch the Video Abstract.

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Section: Anatomy Of N6a‐mtases‐mtase Domainsmentioning

confidence: 99%

Section: Anatomy Of N6a‐mtases‐mtase Domainsmentioning

confidence: 99%

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

2015

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“…TaqI-MTase is composed of two structural motifs, a dsDNA binding domain and an S-adenosyl-L-methionine (AdoMet) binding domain that transfers a methyl group from an AdoMet cofactor to the target adenine residue. In the DNA complex structure, dsDNA is bound at the interface of the two domains with the target adenine extruded from the DNA helix and trapped near into the bound AdoMet cofactor (25). DNA binding clefts in the TRDs could be clearly identified by superpositioning the DNA binding domain of TaqI-MTase to TRD (Fig.…”

Section: Figure Of Merit ϭ ͉͚P(␣)e I␣ ͚͞P(␣)͉ Where P(␣)mentioning

confidence: 99%

Crystal structure of DNA sequence specificity subunit of a type I restriction-modification enzyme and its functional implications

Kim

DeGiovanni

Jancarik

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Type I restriction-modification enzymes are differentiated from type II and type III enzymes by their recognition of two specific dsDNA sequences separated by a given spacer and cleaving DNA randomly away from the recognition sites. They are oligomeric proteins formed by three subunits: a specificity subunit, a methylation subunit, and a restriction subunit. We solved the crystal structure of a specificity subunit from Methanococcus jannaschii at 2.4-Å resolution. Two highly conserved regions (CRs) in the middle and at the C terminus form a coiled-coil of long antiparallel ␣-helices. Two target recognition domains form globular structures with almost identical topologies and two separate DNA binding clefts with a modeled DNA helix axis positioned across the CR helices. The structure suggests that the coiled-coil CRs act as a molecular ruler for the separation between two recognized DNA sequences. Furthermore, the relative orientation of the two DNA binding clefts suggests kinking of bound dsDNA and exposing of target adenines from the recognized DNA sequences. structural genomics ͉ gi 15669898

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“…Such stereochemical positioning was observed for the bound AdoMet. In addition, the M.TaqI-DNA crystal structure implicated the conserved NPPY (DPPY in M.RsrI) motif in activating the exocyclic amino group of the target base so as to accept the methyl group (27). Specifically, the Asn and the second Pro formed hydrogen bonds to the amino group of the flipped adenine base of the target sequence.…”

Section: Adometmentioning

confidence: 99%

Structures of Liganded and Unliganded RsrI N6-Adenine DNA Methyltransferase

Thomas

Scavetta

Gumport

et al. 2003

Journal of Biological Chemistry

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The structures of RsrI DNA methyltransferase (M.RsrI) bound to the substrate S-adenosyl-L-methionine (AdoMet), the product S-adenosyl-L-homocysteine (AdoHcy), the inhibitor sinefungin, as well as a mutant apo-enzyme have been determined by x-ray crystallography. Two distinct binding configurations were observed for the three ligands. The substrate AdoMet adopts a bent shape that directs the activated methyl group toward the active site near the catalytic DPPY motif. The product AdoHcy and the competitive inhibitor sinefungin bind with a straight conformation in which the amino acid moiety occupies a position near the activated methyl group in the AdoMet complex. Analysis of ligand binding in comparison with other DNA methyltransferases reveals a small, common subset of available conformations for the ligand. The structures of M.RsrI with the non-substrate ligands contained a bound chloride ion in the AdoMet carboxylatebinding pocket, explaining its inhibition by chloride salts. The L72P mutant of M.RsrI is the first DNA methyltransferase structure without bound ligand. With respect to the wild-type protein, it had a larger ligandbinding pocket and displayed movement of a loop (223-227) that is responsible for binding the ligand, which may account for the weaker affinity of the L72P mutant for AdoMet. These studies show the subtle changes in the tight specific interactions of substrate, product, and an inhibitor with M.RsrI and help explain how each displays its unique effect on the activity of the enzyme.Biological DNA methylation is ubiquitous and important in many cellular mechanisms including genetic imprinting, immunity, cancer, and gene regulation (1-3). In bacteria, DNA methylation protects the host from foreign DNA through the action of restriction modification systems composed of a restriction endonuclease and a DNA modification methyltransferase (MTase).1 Both enzymes recognize a specific DNA sequence that is usually palindromic. The endonuclease cleaves the DNA unless the MTase has added a methyl group to a base in the recognition sequence. Restriction modification systems are classified by their subunit composition and cofactor requirements (4). The most studied of these classes, type II restriction modification systems, usually have a dimeric endonuclease and a monomeric MTase that requires only the methyl-donating cofactor S-adenosyl-L-methionine (AdoMet) for activity.Type II DNA MTases share a conserved catalytic core structure (5), composed of a seven-␤-stranded sheet flanked by three ␣-helices on each side, that contains the ligand-binding pockets and active site (6, 7). The amino acid sequences of the MTases are not as well conserved as their structures, but they share nine conserved sequence motifs (7). On the basis of these motifs, the MTases are subdivided into C5 MTases, which methylate cytosine at C5, and ␣, ␤, and ␥ subclasses of amino MTases, which methylate either adenine at the N6 position (N6A) or cytosine at the N4 position (N4C) (7). Of the conserved motifs, the catalytic motif IV, w...

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Untitled

Cited by 219 publications

References 27 publications

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

Crystal structure of DNA sequence specificity subunit of a type I restriction-modification enzyme and its functional implications

Structures of Liganded and Unliganded RsrI N6-Adenine DNA Methyltransferase

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