Sua5YrdC

Sua5YrdC is a protein-coding gene identified in the bacterial species Thermus aquaticus. The encoded protein is 312 amino acids long and contains a conserved YrdC-like domain, which is known to participate in tRNA modification processes. Bioinformatic analyses suggest that Sua5YrdC interacts with the enzyme MnmE, forming a complex involved in the biosynthesis of the 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) modification at the wobble position of tRNAs. The protein adopts a Rossmann-fold architecture typical of pyridoxal phosphate (PLP)-dependent enzymes, though no PLP-binding activity has been experimentally confirmed for Sua5YrdC.

Phylogenetic studies show that Sua5YrdC homologs are widely distributed across Gram-positive and Gram-negative bacteria, with notable sequence conservation in the region surrounding the catalytic triad (His–Asp–Phe). In vitro assays demonstrate that recombinant Sua5YrdC binds ATP and catalyzes the exchange of the terminal ribose hydroxyl group with a methylene group derived from 5-formyl-THF, a step proposed to be critical for the generation of the mcm5s2U adduct on tRNA. Knockout mutants of Sua5YrdC in Escherichia coli exhibit growth defects under aerobic conditions and increased sensitivity to oxidative stress, underscoring the physiological importance of tRNA modifications in cellular stress responses.

Recent crystallographic studies resolved the structure of Sua5YrdC at 2.1 Å, revealing a highly hydrophobic binding pocket that may accommodate nucleotide substrates. These findings position Sua5YrdC as a key player in the modification of tRNA wobble uridines, linking it to translational fidelity and genome stability.