Modomics - A Database of RNA Modifications

ID Card:

Full name: tRNA (cytosine(38)-C(5))-methyltransferase
Synonym: Dnmt2
GI: 4758184
Orf: TRDMT1
COG: COG0270
UniProt: O14717
Structures: | 1G55 |
Alpha Fold Predicted Structure: AF-O14717-F1
Enzyme type: methyltransferase
Position of modification - modification: t:38 - m5C


PDB Structures:


1G55

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

DNMT2 is a human protein that displays strong sequence similarities to DNA (cytosine-5)-methyltransferases (m(5)C MTases) of both prokaryotes and eukaryotes. DNMT2 contains all 10 sequence motifs that are conserved among m(5)C MTases, including the consensus S:-adenosyl-L-methionine-binding motifs and the active site ProCys dipeptide. DNMT2 has close homologs in plants, insects and Schizosaccharomyces pombe, but no related sequence can be found in the genomes of Saccharomyces cerevisiae or Caenorhabditis elegans. The crystal structure of a deletion mutant of DNMT2 complexed with S-adenosyl-L-homocysteine (AdoHcy) has been determined at 1.8 A resolution. The structure of the large domain that contains the sequence motifs involved in catalysis is remarkably similar to that of M.HHAI, a confirmed bacterial m(5)C MTase, and the smaller target recognition domains of DNMT2 and M.HHAI are also closely related in overall structure. The small domain of DNMT2 contains three short helices that are not present in M.HHAI. DNMT2 binds AdoHcy in the same conformation as confirmed m(5)C MTases and, while DNMT2 shares all sequence and structural features with m(5)C MTases, it has failed to demonstrate detectable transmethylase activity. We show here that homologs of DNMT2, which are present in some organisms that are not known to methylate their genomes, contain a specific target-recognizing sequence motif including an invariant CysPheThr tripeptide. DNMT2 binds DNA to form a denaturant-resistant complex in vitro. While the biological function of DNMT2 is not yet known, the strong binding to DNA suggests that DNMT2 may mark specific sequences in the genome by binding to DNA through the specific target-recognizing motif.

Download RCSB-PDB Structures:

Pdb Files   1G55.pdb  
Pdbx/mmCIF Files   1G55.cif  


Protein sequence:

MEPLRVLELYSGVGGMHHALRESCIPAQVVAAIDVNTVANEVYKYNFPHTQLLAKTIEGITLEEFDRLSFDMILMSPPCQPFTRIGRQGDMTDSRTNSFLHILDILPRLQKLPKYILLENVKGFEVSSTRDLLIQTIENCGFQYQEFLLSPTSLGIPNSRLRYFLIAKLQSEPLPFQAPGQVLMEFPKIESVHPQKYAMDVENKIQEKNVEPNISFDGSIQCSGKDAILFKLETAEEIHRKNQQDSDLSVKMLKDFLEDDTDVNQYLLPPKSLLRYALLLDIVQPTCRRSVCFTKGYGSYIEGTGSVLQTAEDVQVENIYKSLTNLSQEEQITKLLILKLRYFTPKEIANLLGFPPEFGFPEKITVKQRYRLLGNSLNVHVVAKLIKILYE

Comments:

The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases, including Dnmt1 and Dnmt3 enzymes (Grace Gall et al. 2006 ). DNMT2 contains all 10 sequence motifs that are conserved among m(5)C MTases, including the consensus S:-adenosyl-L-methionine-binding motifs and the active site ProCys dipeptide (Dong et al. 2001 ). It uses the same catalytic residues as other Dnmt enzymes. Nonetheless, DNA methylation activity producing dm5C by Dnmt2 is weak, and both its existence and biological role are controversial. Conversely, Dnmt2 shows robust tRNA Methylation activity yielding to m5C at position 38, in vitro and in vivo . Mammalian substrates include tRNAAsp, tRNAGly, tRNAVal. Dnmt2 homologues are widespread in eukaryotes, including certain single-cellular eukaryotes. Only one bacterial homologue is known, though. Active enzymes have been confirmed in Mammalia, D.melanogaster, S.pombe, and E.histolytica. Through ultraviolet-crosslinking and immunoprecipitation approaches, Müller et al. (2013 ) identified also other weaker substrates for hDnmt2 ( tRNACUC/UUCGly and tRNAGCCGlu) in vitro but not in vivo .




Reaction Substrate SubstrateType Position (Anti)Codon Modified (Anti)Codon Amino Acid Change Transcript Name Transcript Region Cellular Localization References
C:m5C RNA tRNA 38 8UC 8UC tRNAAsp8UC Anticodon Cytoplasm 16424344   
C:m5C RNA tRNA 38 CUC CUC tRNAGluCUC anticodon-loop Cytoplasm 23877245   
C:m5C RNA tRNA 38 UUC UUC tRNAGluUUC anticodon-loop Cytoplasm 23877245   
C:m5C RNA tRNA 38 GCC GCC tRNAGlyGCC anticodon-loop Cytoplasm 23877245   

Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

M E P L R V L E L Y S G V G G M H H A L R E S C I P A Q V V A A I D V N T V A N E V Y K Y N F P H T Q L L A K T I E G I T L E E F D R L S F D M I L M S P P C Q P F T R I G R Q G D M T D S R T N S F L H I L D I L P R L Q K L P K Y I L L E N V K G F E V S S T R D L L I Q T I E N C G F Q Y Q E F L L S P T S L G I P N S R L R Y F L I A K L Q S E P L P F Q A P G Q V L M E F P K I E S V H P Q K Y A M D V E N K I Q E K N V E P N I S F D G S I Q C S G K D A I L F K L E T A E E I H R K N Q Q D S D L S V K M L K D F L E D D T D V N Q Y L L P P K S L L R Y A L L L D I V Q P T C R R S V C F T K G Y G S Y I E G T G S V L Q T A E D V Q V E N I Y K S L T N L S Q E E Q I T K L L I L K L R Y F T P K E I A N L L G F P P E F G F P E K I T V K Q R Y R L L G N S L N V H V V A K L I K I L Y E

Secondary Structure Alphabet

  • G: 3-turn helix (310helix)
  • H: α-helix
  • I: 𝝅-helix (5 - turn helix)
  • T: Hydrogen Bonded Turn
  • B: β-sheet
  • S: Bend
  • C: Coil (residues not present in any of the above conformations)
  • N: Not assigned

Download PDB Structures & DSSP Secondary Structures:

Alpha Fold Pdb Files   AF-O14717-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-O14717-F1.cif  
DSSP Secondary Structures   O14717.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, Golic KG, Jacobsen SE, Bestor TH... Science [details] 16424344 -
Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA. Dong A, Yoder JA, Zhang X, Zhou L, Bestor TH, Cheng X... Nucleic Acids Res [details] 11139614 -

Links:

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