title: Structures and reaction mechanisms of GTP cyclohydrolases.
abstract: GTP cyclohydrolases generate the first committed intermediates for the biosynthesis of certain vitamins/cofactors (folic acid, riboflavin, deazaflavin, and tetrahydrobiopterin), deazapurine antibiotics, some t-RNA bases (queuosine, archaeosine), and the phytotoxin, toxoflavin. They depend on divalent cations for hydrolytic opening of the imidazole ring of the substrate, guanosine triphosphate (GTP). Surprisingly, the ring opening reaction is not the rate-limiting step for GTP cyclohydrolases I and II whose mechanism have been studied in some detail. GTP cyclohydrolase I, Ib, and II are potential targets for novel anti-infectives. Genetic factors modulating the activity of human GTP cyclohydrolase are highly pleiotropic, since the signal transponders whose biosyntheses require their participation (nitric oxide, catecholamines) impact a very wide range of physiological phenomena. Recent studies suggest that human GTP cyclohydrolase may become an oncology target.
authors: Hamburg School of Food Science, Institut für Lebensmittelchemie, Grindelallee 117, 20146 Hamburg, Germany.
authors: Tobias
authors: T
authors: Gräwert
authors: Markus
authors: M
authors: Fischer
authors: Adelbert
authors: A
authors: Bacher
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D001708:Biopterins / Q000031:analogs & derivatives / Q000737:chemistry; D002413:Cations, Divalent / Q000737:chemistry; D004926:Escherichia coli / Q000737:chemistry; D005492:Folic Acid / Q000096:biosynthesis / Q000737:chemistry*; D006136:GTP Cyclohydrolase / Q000737:chemistry*; D006160:Guanosine Triphosphate / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D012256:Riboflavin / Q000096:biosynthesis / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D002413:Cations, Divalent; D001708:Biopterins; D006160:Guanosine Triphosphate; D005492:Folic Acid; D006136:GTP Cyclohydrolase; C003402:sapropterin; D012256:Riboflavin