PreQ0binding

PreQ0 binding refers to the interaction between the queuosine precursor prequeuosine‑0 (PreQ0) and specific enzymes or protein complexes involved in tRNA modification and nucleotide metabolism. PreQ0 is an intermediate formed during the biosynthetic pathway that ultimately generates queuosine, a hypermodified nucleoside found in the wobble position of certain tRNAs. The binding of PreQ0 is a critical regulatory step that ensures proper substrate channeling and fidelity in the queuosine biosynthetic pathway.

In bacteria, the enzyme tRNA guanine transglycosylase (TGT) initially incorporates PreQ0 into tRNA. TGT recognizes the PreQ0 substrate via a conserved pocket that accommodates the cyclopentyl ring and guanine moiety. After insertion, PreQ0 is further converted by enzymes such as queF and queE into a reactive intermediate that is finally transferred to the tRNA by the QueA enzyme. QueA contains a SAM‑dependent adenylation domain that binds both the tRNA substrate and the modified nucleoside, facilitating the transfer of an AMP group to form a unique intermediate.

The structural characterization of PreQ0-binding sites has revealed key residues responsible for substrate specificity, including conserved glycine-rich loops and positively charged residues that stabilize the phosphate backbone of PreQ0. Mutational analysis of these residues often leads to reduced queuosine synthesis, underscoring the functional importance of PreQ0 binding.

Overall, PreQ0 binding is a finely tuned biochemical interaction that coordinates multiple enzymatic steps, ensuring the efficient production of queuosine and contributing to translational accuracy and cellular adaptation to stress.