mnmA

MnmA is a bacterial tRNA-modifying enzyme responsible for the thiolation of uridine at the wobble position 34 in a subset of tRNAs, notably those recognizing lysine, glutamine, and glutamic acid codons. The enzyme catalyzes the final sulfur insertion step that converts the uridine derivative cmnm5U34 into mnm5s2U34, a modification that helps proper codon–anticodon pairing and improves translational accuracy and efficiency.

In the bacterial pathway, the synthesis begins with the formation of cmnm5U34 on tRNA by the MnmE–MnmG (also called TrmE–GidA) complex. MnmA then acts on this substrate to install a sulfur atom, yielding mnm5s2U34. The sulfur donor is the cysteine desulfurase IscS, which transfers sulfur to a catalytic cysteine on MnmA, forming a persulfide intermediate that is subsequently transferred to the tRNA substrate. The catalytic cysteine residue of MnmA, together with ATP-dependent activation of the uridine moiety, enables this thio-modification.

Structurally, MnmA belongs to a family of enzymes that use an active-site cysteine to form covalent intermediates and typically require ATP hydrolysis as part of substrate activation. It functions in concert with MnmG (GidA) and MnmE (TrmE) as part of a conserved bacterial tRNA modification system. The mnm5s2U34 modification enhances decoding of codons ending in A and G and contributes to cellular fitness under stress conditions and varying environmental challenges. In many bacteria, mnmA is essential for optimal growth and translational fidelity.