Function
Cyclohydrolase is an enzyme which catalyzes the reversible cyclization or the ring opening of a purine ring.
• GTP cyclohydrolase I catalyzes the conversion of GTP to 7,8-dihydronepterin triphosphate. GCH I is part of the folate and biopterin biosynthesis[1]
• GTP cyclohydrolase II catalyzes the conversion of GTP to formate, diphosphate and diamino-hydroxy-phosphoribosylamino pyrimidine. GCH II is part of riboflavin metabolism.[2]
• IMP cyclohydrolase catalyzes the conversion of IMP to formido-phosphosibosyl imidazole carboxamide. ICH is part of the purine biosynthesis[3] See also Bifunctional purine biosynthesis protein PURH.
• Methenyltetrahydromethanopterin cyclohydrolase catalyzes the conversion of methenyltetrahydromethanopterin to formyl-tetrahydromethanopterin. MCH is part of the folate biosynthesis[4]
- Methylenetetrahydrofolate dehydrogenase/cyclohydrolase catalyzes the interconversion of 5,10-methylenetetrahydrofolate and 10-formyltetrahydrofolate in mitochondria of mammalian cells.[5]
- Phosphoribosyl AMP-cyclohydrolase catalyzes the third step of His biosynthesis.[6]
Disease
Mutations in GTP cyclohydrolase I are associated with malignant phenylketonuria, hyperphenylalaninemia and DOPA-responsive dystonia.
Structural highlights
GTP cyclohydrolase I from Escherichia coli (1n3r) is pentamer. GCH I GTP binding pocket at the intersubunit interface.[7] Surface representation of GCH I GTP binding pocket.
3D structures of cyclohydrolase
Cyclohydrolase 3D structures
- ↑ Nar H, Huber R, Meining W, Schmid C, Weinkauf S, Bacher A. Atomic structure of GTP cyclohydrolase I. Structure. 1995 May 15;3(5):459-66. PMID:7663943
- ↑ Ren J, Kotaka M, Lockyer M, Lamb HK, Hawkins AR, Stammers DK. GTP cyclohydrolase II structure and mechanism. J Biol Chem. 2005 Nov 4;280(44):36912-9. Epub 2005 Aug 22. PMID:16115872 doi:10.1074/jbc.M507725200
- ↑ Kang YN, Tran A, White RH, Ealick SE. A novel function for the N-terminal nucleophile hydrolase fold demonstrated by the structure of an archaeal inosine monophosphate cyclohydrolase. Biochemistry. 2007 May 1;46(17):5050-62. Epub 2007 Apr 4. PMID:17407260 doi:https://dx.doi.org/10.1021/bi061637j
- ↑ Upadhyay V, Demmer U, Warkentin E, Moll J, Shima S, Ermler U. Structure and catalytic mechanism of N(5),N(10)-methenyl-tetrahydromethanopterin cyclohydrolase. Biochemistry. 2012 Oct 23;51(42):8435-43. doi: 10.1021/bi300777k. Epub 2012 Oct, 8. PMID:23013430 doi:https://dx.doi.org/10.1021/bi300777k
- ↑ Schmidt A, Wu H, MacKenzie RE, Chen VJ, Bewly JR, Ray JE, Toth JE, Cygler M. Structures of three inhibitor complexes provide insight into the reaction mechanism of the human methylenetetrahydrofolate dehydrogenase/cyclohydrolase. Biochemistry. 2000 May 30;39(21):6325-35. PMID:10828945
- ↑ D'Ordine RL, Linger RS, Thai CJ, Davisson VJ. Catalytic zinc site and mechanism of the metalloenzyme PR-AMP cyclohydrolase. Biochemistry. 2012 Jul 24;51(29):5791-803. PMID:22741521 doi:10.1021/bi300391m
- ↑ Rebelo J, Auerbach G, Bader G, Bracher A, Nar H, Hosl C, Schramek N, Kaiser J, Bacher A, Huber R, Fischer M. Biosynthesis of pteridines. Reaction mechanism of GTP cyclohydrolase I. J Mol Biol. 2003 Feb 14;326(2):503-16. PMID:12559918
