Modomics - A Database of RNA Modifications

ID Card:

Full name: Protein O-MannosylTransferase
Synonym: YDL095W
Orf: PMT1
UniProt: P40999
Structures: | 6FDF |
Alpha Fold Predicted Structure: AF-P40999-F1
Enzyme type: methyltransferase

PDB Structures:


Structure Description:


Abstract of the PDB Structure's related Publication:

Dnmt2 methylates cytosine at position 38 of tRNA Asp in a variety of eukaryotic organisms. A correlation between the presence of the hypermodified nucleoside queuosine (Q) at position 34 of tRNA Asp and the Dnmt2 dependent C38 methylation was recently found in vivo for S. pombe and D. discoideum. We demonstrate a direct effect of the Q-modification on the methyltransferase catalytic efficiency in vitro, as V max /K 0.5 of purified S. pombe Dnmt2 shows an increase for in vitro transcribed tRNA Asp containing Q34 to 6.27 ∗ 10 -3  s -1  µM -1 compared to 1.51 ∗ 10 -3  s -1  µM -1 for the unmodified substrate. Q34tRNA Asp exhibits an only slightly increased affinity for Dnmt2 in comparison to unmodified G34tRNA. In order to get insight into the structural basis for the Q-dependency, the crystal structure of S. pombe Dnmt2 was determined at 1.7 Å resolution. It closely resembles the known structures of human and E. histolytica Dnmt2, and contains the entire active site loop. The interaction with tRNA was analyzed by means of mass-spectrometry using UV cross-linked Dnmt2-tRNA complex. These cross-link data and computational docking of Dnmt2 and tRNA Asp reveal Q34 positioned adjacent to the S-adenosylmethionine occupying the active site, suggesting that the observed increase of Dnmt2 catalytic efficiency by queuine originates from optimal positioning of the substrate molecules and residues relevant for methyl transfer.

Download RCSB-PDB Structures:

Pdb Files   6FDF.pdb  
Pdbx/mmCIF Files   6FDF.cif  

Protein sequence:



Dnmt2 orthologs were originally considered to be DNA methylating enzymes, based on their clear sequence homology with other enzymes from a family designated with the abbreviation “Dnmt” for DNA methyltransferase (Jeltsch et al. 2017 ). These enzymes are known for catalyzing cytidine methylation at the carbon-5 position resulting in 5-methylcytosine. Schizosaccharomyces pombe carries a cytosine 5-methyltransferase homolog of the Dnmt2 family (termed pombe methyltransferase 1, Pmt1). It contains no detectable DNA methylation. Pmt1, like other Dnmt2 homologs, has in vitro methylation activity on cytosine 38 of tRNAAsp and, to a lesser extent, of tRNAGlu, despite the fact that it contains a non-consensus residue in catalytic motif IV as compared with its homologs. In vivo tRNA methylation also required Pmt1. Unexpectedly, however, its in vivo activity showed a strong dependence on the nutritional status of the cell because Pmt1-dependent tRNA methylation was induced in cells grown in the presence of peptone or with glutamate as a nitrogen source. Furthermore, this induction required the serine/threonine kinase Sck2, but not the kinases Sck1, Pka1 or Tor1 and was independent of glucose signalling. Taken together, Becker et al. ( 2012) reveals a novel connection between nutrient signalling and tRNA methylation that thus may link tRNA methylation to processes downstream of nutrient signallings like ribosome biogenesis and translation initiation.

Reaction Substrate SubstrateType Position (Anti)Codon Modified (Anti)Codon Amino Acid Change Transcript Name Transcript Region Cellular Localization References
C:m5C RNA tRNA 38 GUC GUC tRNAAspGUC anticodon-loop Cytoplasm 23074192   
C:m5C RNA tRNA 38 UUC UUC tRNAGluUUC anticodon-loop Cytoplasm 23074192   

Alpha Fold Predicted Structure:

Clear Selection and Reset Camera

Protein sequence:

M S E E K T Y K R V E Q D D P V P E L D I K Q G P V R P F I V T D P S A E L A S L R T M V T L K E K L L V A C L A V F T A V I R L H G L A W P D S V V F D E V H F G G F A S Q Y I R G T Y F M D V H P P L A K M L Y A G V A S L G G F Q G D F D F E N I G D S F P S T T P Y V L M R F F S A S L G A L T V I L M Y M T L R Y S G V R M W V A L M S A I C F A V E N S Y V T I S R Y I L L D A P L M F F I A A A V Y S F K K Y E M Y P A N S L N A Y K S L L A T G I A L G M A S S S K W V G L F T V T W V G L L C I W R L W F M I G D L T K S S K S I F K V A F A K L A F L L G V P F A L Y L V F F Y I H F Q S L T L D G D G A S F F S P E F R S T L K N N K I P Q N V V A D V G I G S I I S L R H L S T M G G Y L H S H S H N Y P A G S E Q Q Q S T L Y P H M D A N N D W L L E L Y N A P G E S L T T F Q N L T D G T K V R L F H T V T R C R L H S H D H K P P V S E S S D W Q K E V S C Y G Y S G F D G D A N D D W V V E I D K K N S A P G V A Q E R V I A L D T K F R L R H A M T G C Y L F S H E V K L P A W G F E Q Q E V T C A S S G R H D L T L W Y V E N N S N P L L P E D T K R I S Y K P A S F I S K F I E S H K K M W H I N K N L V E P H V Y E S Q P T S W P F L L R G I S Y W G E N N R N V Y L L G N A I V W W A V T A F I G I F G L I V I T E L F S W Q L G K P I L K D S K V V N F H V Q V I H Y L L G F A V H Y A P S F L M Q R Q M F L H H Y L P A Y Y F G I L A L G H A L D I I V S Y V F R S K R Q M G Y A V V I T F L A A S V Y F F K S F S P I I Y G T P W T Q E L C Q K S Q W L S G W D Y N C N T Y F S S L E E Y K N Q T L T K R E S Q P A A T S T V E E I T I E G D G P S Y E D L M N E D G K K I F K D T E G N E L D P E V V K K M L E E E G A N I L K V E K R A V L 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-P40999-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-P40999-F1.cif  
DSSP Secondary Structures   P40999.dssp  


Title Authors Journal Details PubMed Id DOI
Dynamic modulation of Dnmt2-dependent tRNA methylation by the micronutrient queuine. Müller M, Hartmann M, Schuster I, Bender S, Thüring KL, Helm M, Katze JR, Nellen W, Lyko F, Ehrenhofer-Murray AE. Nucleic Acids Res. [details] 26424849 10.1093/nar/gkv980
Pmt1, a Dnmt2 homolog in Schizosaccharomyces pombe, mediates tRNA methylation in response to nutrient signaling. Maria Becker,Sara Müller,Wolfgang Nellen,Tomasz P Jurkowski,Albert Jeltsch,Ann E Ehrenhofer-Murray Nucleic Acids Res [details] 23074192 -