NADPH-dependent 7-cyano-7-deazaguanine reductase (QueF) (QueF)

NADPH-dependent 7-cyano-7-deazaguanine reductase, commonly referred to as QueF, is an essential enzyme in the de novo biosynthesis of queuosine (Q), a complex modified nucleoside found in the wobble position of tRNAs for Asp, Asn, His, and Tyr (UniProt P0A9M2; Van Lanen et al., 2005). The enzyme catalyzes the NADPH-dependent reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ0) to an amine, forming 7-aminomethyl-7-deazaguanine (preQ1) (EC 1.7.1.13). This step is vital for the subsequent incorporation of the queuosine precursor into tRNA by tRNA-guanine transglycosylase (TGT). Because the queuosine modification is critical for translational fidelity and efficiency in many bacteria, QueF is a significant factor in bacterial fitness and virulence (Yuan et al., 2015). Notably, humans and other eukaryotes lack the biosynthetic pathway for queuosine and must salvage it from their diet or gut flora, making QueF an attractive target for narrow-spectrum antibiotics. Research into QueF inhibitors focuses on small molecules that mimic the preQ0 substrate to block the enzyme's active site. Targeting this enzyme offers a strategy to combat bacterial infections while potentially minimizing off-target effects on human cells, though it may impact the host microbiome.

Other names

7-cyano-7-deazaguanine reductasePreQ0 reductaseQueF proteinQueF-like proteinTGT-related protein

Inhibition of the enzymatic reduction of preQ0 to preQ1, preventing the synthesis of queuosine and thereby disrupting bacterial protein translation fidelity and fitness.