InterPro: IPR016428 Nitrile oxidoreductase, NADPH-dependent, YqcD

This group represents QueF-like proteins, closely related to IPR016856 (QueF/YkvM) but containing an additional N-terminal domain. They are predicted to function as NADPH-dependent nitrile oxidoreductase based on sequence similarity to IPR016856, and to catalyse the NADPH-dependent reduction of 7-cyano-7-deazaguanineto7-aminomethyl-7-deazaguanine, a late step in the biosynthesis of queuosine, a 7-deazaguanine modified nucleoside found in tRNA(GUN) of bacteria and eukaryotes.

Queuosine (Q) is an example of a highly modified nucleoside 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 prokaryotic and eukaryotic phyla [1]. Q is based on a very unusual 7-deazaguanosine core, which is further modified by addition of a cyclopentendiol ring [2].

This group of proteins belongs to the T fold structural superfamily and is related to GTP cyclohydrolase FolE (PIRSF001256). QueF-like proteins form two groups, type I proteins exemplified by Bacillus subtilis YkvM (PIRSF027377) and type II proteins exemplified by Escherichia coli YqcD. 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 [3].

In members of this entry, the N-terminal domain has often been annotated as a membrane-spanning domain, but transmembrane prediction programs run on YqcD do not detect any transmembrane segments [3]. Instead, the QueF motif can be easily detected in this domain, whereas the flanking and invariant cysteine and glutamate residues (Cys-190 and Glu-230 in E. coli YqcD) are only present in the C-terminal domain. The splitting of active-site residues between the two domains of YqcD is very similar to that seen in two-domain FolE, in which neither domain contains the full set of active site residues nor is active when expressed separately. Further, the pattern of active-site splitting is the same in both proteins, with a similarly located conserved central sequence motif split from two flanking sequences, which are 40 residues apart. The splitting of the YqcD active site suggests that a gene duplication occurred, with each domain retaining some of the residues of the putative active site [3]. As in two-domain FolE, such a duplication event and redistribution of active-site residues could allow the YqcD proteins to evolve a simpler quaternary structure than the QueF proteins [3].

For more information on NADPH-dependent nitrile oxidoreductases, please see PIRSF027377.