title: 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 approximately 20% of sequenced bacteria and is prevalent in Archaea, but the family is to this date absent in Eukarya.
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: Basma
authors.initials: B
authors.lastname: El Yacoubi
authors.forename: Shilah
authors.initials: S
authors.lastname: Bonnett
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Anderson
authors.forename: Manal A
authors.initials: MA
authors.lastname: Swairjo
authors.forename: Dirk
authors.initials: D
authors.lastname: Iwata-Reuyl
authors.forename: Valérie
authors.initials: V
authors.lastname: de Crécy-Lagard
mesh_terms: D000150:Acinetobacter / Q000201:enzymology / Q000235:genetics; D000595:Amino Acid Sequence; D001105:Archaea / Q000201:enzymology / Q000235:genetics; D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics; D001419:Bacteria / Q000201:enzymology* / Q000235:genetics; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D006136:GTP Cyclohydrolase / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005798:Genes, Bacterial; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000201:enzymology / Q000235:genetics; D010802:Phylogeny; D011387:Prokaryotic Cells / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D020124:Thermotoga maritima / Q000201:enzymology / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D006136:GTP Cyclohydrolase