InterPro: IPR016856 Nitrile oxidoreductase, NADPH-dependent, QueF

Members of this group are involved in the biosynthesis of queuosine, a 7-deazaguanine-modified nucleoside found in tRNA(GUN) of Bacteria and Eukarya. QueF (YkvM) from Bacillus subtilis has been shown to catalyse the NADPH-dependent reduction of 7-cyano-7-deazaguanine to 7-aminomethyl-7-deazaguanine, a late step in the biosynthesis of queuosine [1].

Queuosine is located in the anticodon wobble position 34 of tRNAs specific for Tyr, His, Asp, and Asn. With few exceptions (such as yeast and mycoplasma), it is widely distributed in most prokaryotes and eukaryotes [2]. Queuosine is based on a very unusual 7-deazaguanosine core, which is further modified by addition of a cyclopentendiol ring [3].

This group of proteins belongs to the T fold structural superfamily and is related to GTP cyclohydrolase (GTP-CH-I) FolE (PIRSF001256). Two major features differentiate the QueF and FolE groups. First, the strictly conserved QueF motif E-78(S/L)K(S/A)hK(L/Y)(Y/F/W)-85 (residue numbers are those of B. subtilis YkvM, h is hydrophobic amino acid) is characteristic of the QueF family, but is not found in the FolE family. Second, four catalytically important residues in FolE [4], His-112, 113, and 179 and Cys-181 (Escherichia coli FolE numbering), are absent in the QueF group.

QueF-like proteins form two groups, type I proteins exemplified by B. subtilis YkvM and type II proteins exemplified by E. coli YqcD (PIRSF004750). The type I proteins are comparable in size with bacterial and mammalian FolE, whereas the type II proteins are larger and are predicted to be comprised of two domains, similar to plant FolE [1].

The discovery of oxidoreductase activity within the FolE scaffold is an intriguing example of structural and functional evolution, particularly in light of the need to bind a second organic substrate, the cofactor NADPH. The specificity of the QueF motif to the QueF family suggests that these residues might be involved in NADPH binding [1]. Additionally, the binding of a modified base to QueF, instead of the nucleotide to FolE, in principle leaves vacant in QueF the binding site occupied by the ribosyl portion of GTP. This putative "empty" ribosyl pocket might also contribute to NADPH binding [1].