Queuine tRNA-ribosyltransferase (TGT) (TGT)

Queuine tRNA-ribosyltransferase (TGT) is a specialized enzyme responsible for the post-transcriptional modification of the wobble position (G34) in tRNAs with GUN anticodons, specifically tRNA-Asn, tRNA-Asp, tRNA-His, and tRNA-Tyr (UniProt: Q9BXR0). The enzyme catalyzes the exchange of a genetically encoded guanine base for the hypermodified base queuosine (Q) in eukaryotes or its precursor pre-queuosine (preQ1) in bacteria (PubMed: 29601181). This modification is essential for maintaining translational fidelity and efficiency, as it optimizes codon-anticodon pairing and prevents ribosomal frameshifting. In humans, the functional enzyme is a heterodimer consisting of a catalytic subunit (QTRT1) and an accessory subunit (QTRT2). TGT has gained attention as a therapeutic target due to its critical role in bacterial virulence and cancer progression. In pathogens like Shigella, TGT is required for the translation of VirF, a master regulator of virulence, making it a validated target for treating shigellosis (PubMed: 25100755). In oncology, many tumors exhibit queuosine-deficient tRNA, which is associated with increased cell proliferation and metastasis, suggesting that restoring or modulating TGT activity could have anti-tumor effects (PubMed: 31433868). While no drugs are currently FDA-approved, small-molecule inhibitors such as lin-benzoguanine derivatives are being actively researched for their antimicrobial and anticancer potential. Additionally, TGT activity is linked to the salvage of queuine from the diet and gut microbiota, and its dysfunction may be involved in neurological and autoimmune disorders.

Other names

tRNA-guanine transglycosylaseGuanine insertion enzymeTGTaseQueuine tRNA-ribosyltransferase 1 (QTRT1)Queuine tRNA-ribosyltransferase catalytic subunit 1

Competitive inhibition of the tRNA-guanine transglycosylation reaction