Reaction: GTP + 4 H2O = formate + 2,5-diamino-6-hydroxy-4-(5-phospho-D-ribosylamino)pyrimidine + 2 phosphate
For diagram of reaction click here
Other name(s): guanosine triphosphate cyclohydrolase II; GTP-8-formylhydrolase; ribA (gene name); GTP 7,8-8,9-dihydrolase (diphosphate-forming)
Systematic name: GTP 7,8-8,9-dihydrolase (formate-releasing, phosphate-releasing)
Comments: The enzyme, found in prokaryotes and some eukaryotes, hydrolytically cleaves the C-N bond at positions 8 and 9 of GTP guanine, followed by a subsequent hydrolytic attack at the base, which liberates formate, and cleavage of the α-β phosphodiester bond of the triphosphate to form diphosphate. The enzyme continues with a slow cleavage of the diphosphate to form two phosphate ions. The enzyme requires zinc and magnesium ions for the cleavage reactions at the GTP guanine and triphosphate sites, respectively. It is one of the enzymes required for flavin biosynthesis in many bacterial species, lower eukaryotes, and plants. cf. EC 3.5.4.16, GTP cyclohydrolase I, EC 3.5.4.29, GTP cyclohydrolase IIa, and EC 3.5.4.39, GTP cyclohydrolase IV.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 56214-35-8
References:
1. Foor, F. and Brown, G.M. Purification and properties of guanosine triphosphate cyclohydrolase II from Escherichia coli. J. Biol. Chem. 250 (1975) 3545-3551. [PMID: 235552]
2. Ritz, H., Schramek, N., Bracher, A., Herz, S., Eisenreich, W., Richter, G. and Bacher, A. Biosynthesis of riboflavin: studies on the mechanism of GTP cyclohydrolase II. J. Biol. Chem. 276 (2001) 22273-22277. [PMID: 11301327]
3. Schramek, N., Bracher, A. and Bacher, A. Biosynthesis of riboflavin. Single turnover kinetic analysis of GTP cyclohydrolase II. J. Biol. Chem. 276 (2001) 44157-44162. [PMID: 11553632]
4. Ren, J., Kotaka, M., Lockyer, M., Lamb, H.K., Hawkins, A.R. and Stammers, D.K. GTP cyclohydrolase II structure and mechanism. J. Biol. Chem. 280 (2005) 36912-36919. [PMID: 16115872]
5. Smith, M.M., Beaupre, B.A., Fourozesh, D.C., Meneely, K.M., Lamb, A.L. and Moran, G.R. Finding ways to relax: a revisionistic analysis of the chemistry of E. coli GTP cyclohydrolase II. Biochemistry 60 (2021) 3027-3039. [PMID: 34569786]