tRNA-guanine transglycosylase (Zymomonas mobilis) (TGT)

tRNA-guanine transglycosylase (TGT) from Zymomonas mobilis is a homodimeric enzyme that plays a critical role in the post-transcriptional modification of tRNA. It catalyzes the site-specific replacement of guanine at the wobble position (G34) of tRNA(Asn, Asp, His, Tyr) with the precursor 7-aminomethyl-7-deazaguanine (preQ1), a key step in the biosynthesis of queuosine (UniProt: P28720). While Z. mobilis is a non-pathogenic bacterium, its TGT is highly homologous to the TGT found in Shigella species, making it a primary structural model for antibiotic drug discovery (PubMed: 10417330). In Shigella, TGT activity is essential for the translation of VirF, the master transcriptional activator of the virulence plasmid, which is required for the invasion of the human intestinal epithelium (PubMed: 12692131). Inhibition of TGT effectively disarms the pathogen by preventing the expression of its virulence machinery without necessarily killing the bacteria, potentially reducing the pressure for resistance (PubMed: 25654371). Numerous small-molecule inhibitors, particularly those based on the lin-benzoguanine scaffold, have been developed and characterized using the Z. mobilis enzyme as a surrogate (PubMed: 21417383).

Other names

Queuine tRNA-ribosyltransferaseGuanine insertion enzymetRNA-guanine 7-guanine transferaseZmTGT

Inhibition of the exchange of guanine with pre-queuosine (preQ1) at position 34 of tRNA, preventing the formation of queuosine-modified tRNA required for the translation of virulence factors.