Queuine tRNA-ribosyltransferase (Zymomonas mobilis) (TGT)

Queuine tRNA-ribosyltransferase (TGT) from Zymomonas mobilis is a well-characterized bacterial enzyme that serves as a primary model for studying the biosynthesis of queuosine (Q), a hypermodified nucleoside found in the wobble position of tRNAs for Asp, Asn, His, and Tyr (UniProt P28720). The enzyme catalyzes the base-exchange reaction where guanine at position 34 is replaced by 7-aminomethyl-7-deazaguanine (preQ1), a critical step in bacterial tRNA maturation (PubMed: 10417320). While Z. mobilis itself is not a human pathogen, its TGT is structurally homologous to TGTs in pathogens like Shigella flexneri, where the enzyme is essential for the translation of VirF, a master regulator of virulence (PubMed: 15590635). Consequently, TGT is a significant target for the development of narrow-spectrum antibiotics aimed at treating shigellosis and other infections by inhibiting bacterial virulence without necessarily killing the bacteria or affecting the host's microbiome (PubMed: 21838330). Drug discovery efforts have focused on small-molecule inhibitors, such as lin-benzoguanine derivatives, which occupy the guanine-binding pocket to block enzymatic activity (PubMed: 11551199).

Other names

tRNA-guanine transglycosylasetRNA-guanine(34) transglycosylaseGuanine insertion enzymetRNA-ribosyltransferase-guanineQueuine tRNA-ribosyltransferase 1

Inhibition of the exchange of guanine 34 in the anticodon wobble position of tRNA with 7-aminomethyl-7-deazaguanine (preQ1), thereby preventing the formation of queuosine-modified tRNA which is essential for the translation of virulence factors in certain pathogenic bacteria.