page_title: DNA adenine methylase
section_title: Structural features
hierarchical_section_title: DNA adenine methylase / Structural features
caption_attribution_description: English: An image of E.coli DNA adenine methyltransferase is displayed here using PDB identifier 2G1P. The catalytically competent methylase is shown here bound to duplex DNA with the target adenine base represented by a blue stick, flipped out of the active site in the presence of the inhibitor, sinefungin.
context_page_description: DNA adenine methylase, is an enzyme that adds a methyl group to the adenine of the sequence 5'-GATC-3' in newly synthesized DNA. Immediately after DNA synthesis, the daughter strand remains unmethylated for a short time. It is an orphan methyltransferase that is not part of a restriction-modification system and regulates gene expression. This enzyme catalyses the following chemical reaction
  S-adenosyl-L-methionine + DNA adenine S-adenosyl-L-homocysteine + DNA 6-methylaminopurine
  This is a large group of enzymes unique to prokaryotes and bacteriophages.
  The E. coli DNA adenine methyltransferase enzyme, is widely used for the chromatin profiling technique, DamID. In which the Dam is fused to a DNA-binding protein of interest and expressed as a transgene in a genetically tractable model organism to identify protein binding sites.
context_section_description: The similarity in the catalytic domains of C5-cytosine methyltransferases and N6 and N4-adenine methyltransferases provided great interest in understanding the basis for functional similarities and dissimilarities. The methyltransferases or methylases are classified into three groups (Groups α, β, and γ) based on the sequential order of certain 9 motifs and the Target Recognition Domain (TRD). Motif I consists of a Gly-X-Gly tripeptide and is referred to as the G-loop and is implicated in the binding of the S-Adenosyl methionine cofactor. Motif II is highly conserved among N4 and N6-adenine methylases and contains a negatively charged amino acid followed by a hydrophobic side chain in the last positions of the β2 strand to bind the AdoMet. Motif III is also implicated in the binding of Adomet. Motif IV is especially important and well known in methylase characterizations. It consists of a diprolyl component and is highly conserved among N6-adenine methyltransferases as the DPPY motif, however, this motif can vary for N4-adenine and C5-cytosine methyltransferases. The DPPY motif has been found to be essential for AdoMet binding. Motifs IV-VIII play a role in the catalytic activity, while motifs 1-III and X play a role in binding of the cofactor. For N6-adenine methylases the sequential order for these motifs is as such: N-terminal - X - I - II - III - TRD - IV - V - VI - VII - VIII - C-terminal and E. coli Dam methylase follows this structural sequence. A 2015 crystallography experiment showed that E. coli Dam methylase was able to bind non-GATC DNA with the same sequence of motifs discussed; the authors posit that the obtained structure could serve as grounds for repression of transcription that is not methylation based.
caption: The X-ray crystal structure of E. coli Dam methylase shows the enzyme bound to double-stranded DNA and the inhibitor sinefungin. The adenine to be modified is shown as a blue stick flipped out of the double helix and towards the enzyme's interior.
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