tRNA-guanine transglycosylase (TGT) (TGT)

tRNA-guanine transglycosylase (TGT) from Escherichia coli is a key enzyme involved in the post-transcriptional modification of tRNA. It catalyzes the exchange of a guanine base at the wobble position (position 34) of tRNAs (specifically tRNA-Asn, -Asp, -His, and -Tyr) with the 7-deazaguanine precursor 7-aminomethyl-7-deazaguanine (preQ1) [1.2.1]. This reaction is the first step in the biosynthesis of queuosine, a hypermodified nucleoside found in all domains of life except archaea, which is essential for translational fidelity [1.1.2]. In pathogenic bacteria like Shigella flexneri, TGT is essential for virulence because it modifies the mRNA of the transcriptional regulator VirF, which is required for the expression of invasion factors [1.3.3]. Inhibiting TGT leads to a loss of pathogenicity, making it a promising target for treating shigellosis and other enteric infections [1.3.1]. Because the bacterial enzyme functions as a homodimer and uses preQ1 as a substrate, while the human version is a heterodimer that uses queuine, there is a significant opportunity for selective drug design [1.1.3]. Several classes of small-molecule inhibitors, including quinazolinones and lin-benzoguanines, have been developed to target the enzyme's active site and block its activity [1.4.3]. These inhibitors represent a novel class of anti-virulence agents that could provide an alternative to traditional antibiotics [1.4.2].

Other names

Queuine tRNA-ribosyltransferaseGuanine insertion enzymetgtvacC

Inhibition of the base-exchange reaction catalyzed by TGT, preventing the incorporation of preQ1 into tRNA and the modification of virulence-related mRNA, thereby suppressing the expression of bacterial invasion factors.