Modomics - A Database of RNA Modifications

ID Card:

Full name: tRNA (uridine-5-oxyacetic acid methyl ester)(34) synthase
Synonym: YecO
GI: 3025151
Orf: b1870
COG: COG2226
UniProt: P76290
Structures: | 4GEK | 4IWN |
Alpha Fold Predicted Structure: AF-P76290-F1
Enzyme type: methyltransferase
Position of modification - modification: t:34 - cmo5U
t:34 - mcmo5U


PDB Structures:


4GEK

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

The identification of novel metabolites and the characterization of their biological functions are major challenges in biology. X-ray crystallography can reveal unanticipated ligands that persist through purification and crystallization. These adventitious protein-ligand complexes provide insights into new activities, pathways and regulatory mechanisms. We describe a new metabolite, carboxy-S-adenosyl-l-methionine (Cx-SAM), its biosynthetic pathway and its role in transfer RNA modification. The structure of CmoA, a member of the SAM-dependent methyltransferase superfamily, revealed a ligand consistent with Cx-SAM in the catalytic site. Mechanistic analyses showed an unprecedented role for prephenate as the carboxyl donor and the involvement of a unique ylide intermediate as the carboxyl acceptor in the CmoA-mediated conversion of SAM to Cx-SAM. A second member of the SAM-dependent methyltransferase superfamily, CmoB, recognizes Cx-SAM and acts as a carboxymethyltransferase to convert 5-hydroxyuridine into 5-oxyacetyl uridine at the wobble position of multiple tRNAs in Gram-negative bacteria, resulting in expanded codon-recognition properties. CmoA and CmoB represent the first documented synthase and transferase for Cx-SAM. These findings reveal new functional diversity in the SAM-dependent methyltransferase superfamily and expand the metabolic and biological contributions of SAM-based biochemistry. These discoveries highlight the value of structural genomics approaches in identifying ligands within the context of their physiologically relevant macromolecular binding partners, and in revealing their functions.

Download RCSB-PDB Structures:

Pdb Files   4GEK.pdb   4IWN.pdb  
Pdbx/mmCIF Files   4GEK.cif   4IWN.cif  


Protein sequence:

MSHRDTLFSAPIARLGDWTFDERVAEVFPDMIQRSVPGYSNIISMIGMLAERFVQPGTQVYDLGCSLGAATLSVRRNIHHDNCKIIAIDNSPAMIERCRRHIDAYKAPTPVDVIEGDIRDIAIENASMVVLNFTLQFLEPSERQALLDKIYQGLNPGGALVLSEKFSFEDAKVGELLFNMHHDFKRANGYSELEISQKRSMLENVMLTDSVETHKARLHNAGFEHSELWFQCFNFGSLVALKAEDAA

Comments:

CmoA is involved in the formation of cmo(5)U. It was annotated as an S-adenosyl-Lmethonin dependent (SAM-dependent) methyltransferase, given its sequence homology with SAM-contianing-enzymes (Byrne et al. 2013 ). Nevertheless, a novel S-adenosyl-S-carboxymethyl-L-homocysteine factor was observed along its sequence in which the donor methyl group is substituted by a carboxymethyl group. This has suggested the reannotation of ComA to SCM-SHA and not SAM (Byrne et al. 2013 ).

CmoA targets tRNAPro. Null mutations of CmoA bring to the accumulation of 5-methoxyuridine (mo5U34) and ho5U34 and the absence of cmo5U34. The presence of these modifications brings to a reduced reading activity of tRNAPro. Indeed, these results suggest that cmoA is directly involved in the carboxymethylation of ho5U34 to cmo5U34 as the final step of a reaction pathway that involves modification of U34 to ho5U34 by unidentified enzymes and hoU34 to mo5U by CmoB (Nasvall et al. 2013 ).





Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

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

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-P76290-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-P76290-F1.cif  
DSSP Secondary Structures   P76290.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
The modified wobble nucleoside uridine-5-oxyacetic acid in tRNAPro(cmo5UGG) promotes reading of all four proline codons in vivo. Nasvall SJ, Chen P, Bjork GR RNA [details] 15383682 -
The wobble hypothesis revisited: uridine-5-oxyacetic acid is critical for reading of G-ending codons. Nasvall SJ, Chen P, Bjork GR RNA [details] 17942742 -
A novel link between the biosynthesis of aromatic amino acids and transfer RNA modification in Escherichia coli. Bjork GR J Mol Biol [details] 6160251 -
Structure-guided discovery of the metabolite carboxy-SAM that modulates tRNA function. Kim J, Xiao H, Bonanno JB, Kalyanaraman C, Brown S, Tang X, Al-Obaidi NF, Patskovsky Y, Babbitt PC, Jacobson MP, Lee YS, Almo SC... Nature [details] 23676670 -
S-Adenosyl-S-carboxymethyl-L-homocysteine: a novel cofactor found in the putative tRNA-modifying enzyme CmoA. Byrne RT, Whelan F, Aller P, Bird LE, Dowle A, Lobley CM, Reddivari Y, Nettleship JE, Owens RJ, Antson AA, Waterman DG... Acta Crystallogr D Biol Crystallogr [details] 23695253 -

Links:

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