InterPro domain: IPR043133

GTP cyclohydrolase I ( 3.5.4.16 ) catalyses the biosynthesis of formic acid and dihydroneopterin triphosphate from GTP [ 1 ]. 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 comparison of the sequence of the enzyme from bacterial and eukaryotic sources shows that the structure of this enzyme has been extremely well conserved throughout evolution [ 2 ].

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 catalyses the reduction of the nitrile group of 7-cyano-7-deazaguanine to 7-aminomethyl-7-deazaguanine [ 3 , 4 ]. 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 (GTP-CH-I), which has been well conserved throughout evolution across bacterial and eukaryotic species. The C-terminal domain contains the regions relevant for oligomerisation and enzyme catalysis. The structure of the C-terminal domain of GTP-CH-I is topologically identical to PTPS (6-pyruvoyl tetrahydropterin synthase), despite the lack of sequence homology with PTPS [ 5 ]. The superfamily also includes a domain from NADPH-dependent 7-cyano-7-deazaguanine reductase (QueF). This domain is composed of a three-stranded beta-sheet and two alpha-helices.

1. Biosynthesis of pteridines. Reaction mechanism of GTP cyclohydrolase I. J. Mol. Biol. 326, 503-16
2. Homology cloning of GTP-cyclohydrolase I from various unrelated eukaryotes by reverse-transcription polymerase chain reaction using a general set of degenerate primers. Biochem. Biophys. Res. Commun. 212, 705-11
3. High-resolution structure of the nitrile reductase QueF combined with molecular simulations provide insight into enzyme mechanism. J. Mol. Biol. 404, 127-37
4. Structural basis of biological nitrile reduction. J. Biol. Chem. 287, 30560-70
5. Atomic structure of GTP cyclohydrolase I. Structure 3, 459-66