GTP cyclohydrolase I catalyses the biosynthesis of formic acid and dihydroneopterin triphosphate from GTP. This reaction is the first step in the biosynthesis of tetrahydrofolate in prokaryotes, of tetrahydrobiopterin in vertebrates, and of pteridine-containing pigments in insects. The enzyme is a homodecameric complex (a dimer of pentamers) containing one zinc ion per subunit. The pentamerisation leads to the formation of a 20-stranded antiparallel beta-barrel.

The QueF (NADPH-dependent 7-cyano-7-deazaguanine reductase) monomer is made up of two ferredoxin-like domains aligned together with their beta-sheets that have additional embellishments. QueF catalyzes the reduction of the nitrile group of 7-cyano-7-deazaguanine to 7-aminomethyl-7-deazaguanine. QueF reduces a nitrile bond to a primary amine. The two monomer units together create suitable substrate-binding pockets.

This superfamily entry consists of the C-terminal domain found in GTP cyclohydrolases I, which has been well conserved throughout evolution across bacterial and eukaryotic species. The C-terminal domain containing the regions relevant for oligomerisation and enzyme catalysis. The structure of the C-terminal domain of GTP-CH-I is topologically identical to PTPS, despite the lack of sequence homology with 6-pyruvoyl tetrahydropterin synthase (PTPS). The superfamily also includes the N-terminal domain from NADPH-dependent 7-cyano-7-deazaguanine reductase (QueF). The N-terminal domain is composed of a three-stranded beta-sheet and two alpha-helices.

PFAM:PF01227, INTERPRO:IPR020602, INTERPRO:IPR001474, INTERPRO:IPR029139,PMID:12559918,PMID:7663943,PMID:20875425,PMID:22787148