Reaction: GTP + S-adenosyl-L-methionine + reduced electron acceptor = (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate + 5'-deoxyadenosine + L-methionine + oxidized electron acceptor
For diagram of reaction click here.
Other name(s): MOCS1A (gene name); moaA (gene name); cnx2 (gene name)
Systematic name: GTP 3',8-cyclase [(8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate-forming]
Comments: The enzyme catalyses an early step in the biosynthesis of the molybdenum cofactor (MoCo). In bacteria and plants the reaction is catalysed by MoaA and Cnx2, respectively. In mammals it is catalysed by the MOCS1A domain of the bifunctional MOCS1 protein, which also catalyses EC 4.6.1.17, cyclic pyranopterin monophosphate synthase. The enzyme belongs to the superfamily of radical S-adenosyl-L-methionine (radical SAM) enzymes, and contains two oxygen-sensitive FeS clusters.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Hänzelmann, P., Hernandez, H.L., Menzel, C., Garcia-Serres, R., Huynh, B.H., Johnson, M.K., Mendel, R.R. and Schindelin, H. Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis. J. Biol. Chem. 279 (2004) 34721-34732. [PMID: 15180982]
2. Hänzelmann, P. and Schindelin, H. Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans. Proc. Natl. Acad. Sci. USA 101 (2004) 12870-12875. [PMID: 15317939]
3. Hänzelmann, P. and Schindelin, H. Binding of 5'-GTP to the C-terminal FeS cluster of the radical S-adenosylmethionine enzyme MoaA provides insights into its mechanism. Proc. Natl. Acad. Sci. USA 103 (2006) 6829-6834. [PMID: 16632608]
4. Lees, N.S., Hänzelmann, P., Hernandez, H.L., Subramanian, S., Schindelin, H., Johnson, M.K. and Hoffman, B.M. ENDOR spectroscopy shows that guanine N1 binds to [4Fe-4S] cluster II of the S-adenosylmethionine-dependent enzyme MoaA: mechanistic implications. J. Am. Chem. Soc. 131 (2009) 9184-9185. [PMID: 19566093]
5. Hover, B.M., Loksztejn, A., Ribeiro, A.A. and Yokoyama, K. Identification of a cyclic nucleotide as a cryptic intermediate in molybdenum cofactor biosynthesis. J. Am. Chem. Soc. 135 (2013) 7019-7032. [PMID: 23627491]
6. Hover, B.M. and Yokoyama, K. C-Terminal glycine-gated radical initiation by GTP 3',8-cyclase in the molybdenum cofactor biosynthesis. J. Am. Chem. Soc. 137 (2015) 3352-3359. [PMID: 25697423]
7. Hover, B.M., Tonthat, N.K., Schumacher, M.A. and Yokoyama, K. Mechanism of pyranopterin ring formation in molybdenum cofactor biosynthesis. Proc. Natl. Acad. Sci. USA 112 (2015) 6347-6352. [PMID: 25941396]