Modomics - A Database of RNA Modifications

ID Card:

Full name: tRNA uridine 5-carboxymethylaminomethyl modification enzyme MnmG
Synonym: GidA
GI: 15606146
COG: COG0445
UniProt: O66962
Structures: | 2ZXH | 2ZXI |
Alpha Fold Predicted Structure: AF-O66962-F1
Complex: MnmG/MnmE
Enzyme type: other
Position of modification - modification: t:34 - cmnm5s2U
t:34 - cmnm5U


PDB Structures:


2ZXH

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

The 5-carboxymethylaminomethyl modification of uridine (cmnm(5)U) at the anticodon first position occurs in tRNAs that read split codon boxes ending with purine. This modification is crucial for correct translation, by restricting codon-anticodon wobbling. Two conserved enzymes, GidA and MnmE, participate in the cmnm(5)U modification process. Here we determined the crystal structure of Aquifex aeolicus GidA at 2.3 A resolution. The structure revealed the tight interaction of GidA with FAD. Structure-based mutation analyses allowed us to identify two conserved Cys residues in the vicinity of the FAD-binding site that are essential for the cmnm(5)U modification in vivo. Together with mutational analysis of MnmE, we propose a mechanism for the cmnm(5)U modification process where GidA, but not MnmE, attacks the C6 atom of uridine by a mechanism analogous to that of thymidylate synthase. We also present a tRNA-docking model that provides structural insights into the tRNA recognition mechanism for efficient modification.

Download RCSB-PDB Structures:

Pdb Files   2ZXH.pdb   2ZXI.pdb  
Pdbx/mmCIF Files   2ZXH.cif   2ZXI.cif  


Protein sequence:

MAWVVDEFDVVVIGGGHAGIEAALAAARMGAKTAMFVLNADTIGQMSCNPAIGGIAKGIVVREIDALGGEMGKAIDQTGIQFKMLNTRKGKAVQSPRAQADKKRYREYMKKVCENQENLYIKQEEVVDIIVKNNQVVGVRTNLGVEYKTKAVVVTTGTFLNGVIYIGDKMIPGGRLGEPRSEGLSDFYRRFDFPLIRFKTGTPARLDKRTIDFSALEVAPGDDPPPKFSFWTEPVGSYWFPKGKEQVNCWITYTTPKTHEIIRKNLHRTALYGGLIKGIGPRYCPSIEDKIVKFPDKERHQIFLEPEGLDTIEIYPNGLSTSLPEEVQWEMYRSIPGLENVVLIRPAYAIEYDVVPPTELYPTLETKKIRGLFHAGNFNGTTGYEEAAGQGIVAGINAALRAFGKEPIYLRRDESYIGVMIDDLTTKGVTEPYRLFTSRSEYRLYIRQDNAILRLAKLGRELGLLSEEQYKLVKELEREIEKWKEFYKSERVSVAVGGDTRSYSVATLMTMNYTLDDVKEKFGYEVPQHPYVKEEVEIQLKYEPYIERERKLNEKLKKLEDTKIPPDIDYDKIPGLTKEAREKLKKFKPITVGQASRIDGITPAAITALLVYLGKLD

Comments:

Homologue of E. coli MnmG. Flavoprotein, using methyl-(or methylen)-tetrahydrofolate as a donor of one carbon. In a complex with GTPase MnmE they catalyze the formation of either cmnm5U or nm5U by reacting either with glycine or with ammonium.




Reaction Substrate SubstrateType Position (Anti)Codon Modified (Anti)Codon Amino Acid Change Transcript Name Transcript Region Cellular Localization References
Um:cmnm5Um RNA tRNA 34 JUC )UC tRNAGuUUC wobble - position Prokaryotic Cytosol 19446527   
s2U:nm5s2U RNA tRNA 34 2UC ∫UC tRNAGlu2UC wobble - position Prokaryotic Cytosol 19446527   
se2U:nm5se2U RNA tRNA 34 ωUC πUC tRNAGluωUC wobble - position Prokaryotic Cytosol 19446527   
s2U:cmnm5s2U RNA tRNA 34 2UC $UC tRNAGlu2UC wobble - position Prokaryotic Cytosol 19446527   
se2U:cmnm5se2U RNA tRNA 34 ωUC ⊥UC tRNAGluωUC wobble - position Prokaryotic Cytosol 19446527   
U:nm5U tRNA (t) tRNA 34 UUC ∪UC tRNAGluUUC wobble - position Prokaryotic Cytosol 19446527   
U:cmnm5U RNA tRNA 34 UUC !UC tRNAGluUUC wobble - position Prokaryotic Cytosol 19446527   

Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

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

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-O66962-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-O66962-F1.cif  
DSSP Secondary Structures   O66962.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
Conserved cysteine residues of GidA are essential for biogenesis of 5-carboxymethylaminomethyluridine at tRNA anticodon. Osawa T, Ito K, Inanaga H, Nureki O, Tomita K, Numata T Structure [details] 19446527 -
Enzymology of tRNA modification in the bacterial MnmEG pathway. Armengod ME, Moukadiri I, Prado S, Ruiz-Partida R, Benitez-Paez A, Villarroya M, Lomas R, Garzon MJ, Martinez-Zamora A, Meseguer S, Navarro-Gonzalez C Biochimie [details] 22386868 -
SAXS analysis of the tRNA-modifying enzyme complex MnmE/MnmG reveals a novel interaction mode and GTP-induced oligomerization. Fislage M, Brosens E, Deyaert E, Spilotros A, Pardon E, Loris R, Steyaert J, Garcia-Pino A, Versees W... Nucleic Acids Res [details] 24634441 -

Links:

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