Modomics - A Database of RNA Modifications

ID Card:

Full name: tRNA (uracil-5-)-methyltransferase homolog A
Synonym: HpaII tiny fragments locus 9c protein
GI: 51316479
UniProt: Q8IZ69
Structures: | 7NTN | 7NTO |
Alpha Fold Predicted Structure: AF-Q8IZ69-F1
Complex: none
Enzyme type: methyltransferase


PDB Structures:


7NTN

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

Polyglutamine (polyQ) diseases are characterized by an expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats encoding for an uninterrupted prolonged polyQ tract. We previously identified TRMT2A as a strong modifier of polyQ-induced toxicity in an unbiased large-scale screen in Drosophila melanogaster . This work aimed at identifying and validating pharmacological TRMT2A inhibitors as treatment opportunities for polyQ diseases in humans. Computer-aided drug discovery was implemented to identify human TRMT2A inhibitors. Additionally, the crystal structure of one protein domain, the RNA recognition motif (RRM), was determined, and Biacore experiments with the RRM were performed. The identified molecules were validated for their potency to reduce polyQ aggregation and polyQ-induced cell death in human HEK293T cells and patient derived fibroblasts. Our work provides a first step towards pharmacological inhibition of this enzyme and indicates TRMT2A as a viable drug target for polyQ diseases.

Download RCSB-PDB Structures:

Pdb Files   7NTN.pdb   7NTO.pdb  
Pdbx/mmCIF Files   7NTN.cif   7NTO.cif  


Protein sequence:

MSENLDNEGPKPMESCGQESSSALSCPTVSVPPAAPAALEEVEKEGAGAATGPGPQPGLYSYIRDDLFTSEIFKLELQNVPRHASFSDVRRFLGRFGLQPHKTKLFGQPPCAFVTFRSAAERDKALRVLHGALWKGRPLSVRLARPKADPMARRRRQEGESEPPVTRVADVVTPLWTVPYAEQLERKQLECEQVLQKLAKEIGSTNRALLPWLLEQRHKHNKACCPLEGVRPSPQQTEYRNKCEFLVGVGVDGEDNTVGCRLGKYKGGTCAVAAPFDTVHIPEATKQVVKAFQEFIRSTPYSAYDPETYTGHWKQLTVRTSRRHQAMAIAYFHPQKLSPEELAELKTSLAQHFTAGPGRASGVTCLYFVEEGQRKTPSQEGLPLEHVAGDRCIHEDLLGLTFRISPHAFFQVNTPAAEVLYTVIQDWAQLDAGSMVLDVCCGTGTIGLALARKVKRVIGVELCPEAVEDARVNAQDNELSNVEFHCGRAEDLVPTLVSRLASQHLVAILDPPRAGLHSKVILAIRRAKNLRRLLYVSCNPRAAMGNFVDLCRAPSNRVKGIPFRPVKAVAVDLFPQTPHCEMLILFERVEHPNGTGVLGPHSPPAQPTPGPPDNTLQETGTFPSS

Comments:

TRMT2A methylates U54 of cytosolic tRNAs





Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

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

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-Q8IZ69-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q8IZ69-F1.cif  
DSSP Secondary Structures   Q8IZ69.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
FICC-Seq: a method for enzyme-specified profiling of methyl-5-uridine in cellular RNA. Jean-Michel Carter,Warren Emmett,Igor Rdl Mozos,Annika Kotter,Mark Helm,Jernej Ule,Shobbir Hussain Nucleic Acids Res [details] 31361898 -
mU54 tRNA Hypomodification by Lack of TRMT2A Drives the Generation of tRNA-Derived Small RNAs. Marisa Pereira,Diana R Ribeiro,Miguel M Pinheiro,Margarida Ferreira,Stefanie Kellner,Ana R Soares Int J Mol Sci [details] 33799331 -