Discovery of a New Prokaryotic Type I GTP Cyclohydrolase Family

Abstract

GTP cyclohydrolase I (GCYH-I) is the first enzyme of the de novo tetrahydrofolate biosynthetic pathway present in bacteria, fungi, and plants, and encoded in Escherichia coli by the folE gene. It is also the first enzyme of the biopterin (BH4) pathway in Homo sapiens, where it is encoded by a homologous folE gene. A homology-based search of GCYH-I orthologs in all sequenced bacteria revealed a group of microbes, including several clinically important pathogens, that encoded all of the enzymes of the tetrahydrofolate biosynthesis pathway but GCYH-I, suggesting that an alternate family was present in these organisms. A prediction based on phylogenetic occurrence and physical clustering identified the COG1469 family as a potential candidate for this missing enzyme family. The GCYH-I activity of COG1469 family proteins from a variety of sources (Thermotoga maritima, Bacillus subtilis, Acinetobacter baylyi, and Neisseria gonorrhoeae) was experimentally verified in vivo and/or in vitro. Although there is no detectable sequence homology with the canonical GCYH-I, protein fold recognition based on sequence profiles, secondary structure, and solvation potential information suggests that, like GCYH-I proteins, COG1469 proteins are members of the tunnel-fold (T-fold) structural superfamily. This new GCYH-I family is found in ϳ20% of sequenced bacteria and is prevalent in Archaea, but the family is to this date absent in Eukarya.

Identification of Salmonella enterica Serovar Pullorum Antigenic Determinants Expressed In Vivo

“…IVIAT also indentified enzymes involved in the synthesis of cell molecules, including amino acids, pyrimidine, and alginate. These results are consistent with those discovered using IVIAT with other organisms (12,(17)(18)(19)(20)(21), including identical proteins and proteins with a similar function, such as folE, which is a GTP cyclohydrolase I essential for folate synthesis (35), and narV, narY, and narW, which are located in the narZYWV locus encoding nitrate reductase 2 and are involved in the biochemical reaction of reducing nitrate (36).…”

Characterization of the Response to Zinc Deficiency in the Cyanobacterium Anabaena sp. Strain PCC 7120

“…Thus, the derepression of all4725 under zinc limitation would probably lead to the replacement of a zinc-dependent porphobilinogen synthase (All4380) by a zinc-independent one (All4725), under conditions in which the former is most probably inactive. Replacement of zinc-dependent proteins by zinc-independent isoforms seems to be a common strategy in a variety of prokaryotes (5,16,21,31,50).…”

A Gateway platform for functional genomics in Haloferax volcanii: deletion of three tRNA modification genes

“…Haloferax volcanii is one of the rare archaea with both active folate and G + pathways (Gupta 1984, Gupta 1986, Ortenberg et al 2000; however, no folE gene has been identified in its genome. Instead, H. volcanii possesses a folE2 gene (HVO_2348) encoding a newly discovered GTP cyclohydrolase enzyme IB that is involved in archaeosine biosynthesis (El Yacoubi et al 2006, Phillips et al 2008. A role in folate biosynthesis has yet to be demonstrated.…”