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Literature summary extracted from

  • Maita, N.; Hatakeyama, K.; Okada, K.; Hakoshima, T.
    Structural basis of biopterin-induced inhibition of GTP cyclohydrolase I by GFRP, its feedback regulatory proteins (2004), J. Biol. Chem., 279, 51534-51540.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
3.5.4.16 L-phenylalanine stimulates the enzyme via mediation of GFRP which forms a complex with the enzyme Rattus norvegicus

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
3.5.4.16 crystallization of purified recombinant enzyme and protein GFRP forming a BH2-induced inhibitory complex, involving dGTP, in 14% isopropanol, 0.2 M ammonium sulfate, 10% PEG 300, 10% ethylene glycol, 0.1 M MES-Na, pH 6.0, rapid freezing of crystals in liquid nitrogen, X-ray diffraction structure determination and analysis at 2.8 A resolution Rattus norvegicus

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.5.4.16 dihydrobiopterin induction of feedback inhibition, binding site structure Rattus norvegicus
3.5.4.16 tetrahydrobiopterin induction of feedback inhibition of the enzyme via mediation of GFRP which forms a complex with the enzyme, binding site structure Rattus norvegicus

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
3.5.4.16 Zn2+ 1 ion per active site Rattus norvegicus

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
3.5.4.16 50000
-
 GFRP Rattus norvegicus
3.5.4.16 260000
-
 GTP cyclohydrolase I Rattus norvegicus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.5.4.16 GTP + H2O Rattus norvegicus rate-limiting step in the biosynthesis of tetrahydrobiopterin, a key factor necessary for nitric oxide synthase, and for the hydrolxylases that are involved in the production of catecholamines and serotonin formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
 ?
3.5.4.16 additional information Rattus norvegicus enzyme deficiency causes hyperphenylalaninemia with severe neurological disorders, the 3,4-dihydroxyphenylalanine, i.e. DOPA, responsive form of dystonia, and endothelial dysfunction, all by (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin depletion, the GTP cyclohydrolase I feedback regulatory protein GFRP binds to the enzyme and mediates the regulation of the enzyme by L-phenylalanine and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.5.4.16 Rattus norvegicus
-
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
3.5.4.16 GTP + H2O = formate + 7,8-dihydroneopterin 3'-triphosphate allosteric regulation mechanism, active site structure Rattus norvegicus
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.5.4.16 GTP + H2O
-
 Rattus norvegicus formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
 ?
3.5.4.16 GTP + H2O rate-limiting step in the biosynthesis of tetrahydrobiopterin, a key factor necessary for nitric oxide synthase, and for the hydrolxylases that are involved in the production of catecholamines and serotonin Rattus norvegicus formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
 ?
3.5.4.16 additional information enzyme deficiency causes hyperphenylalaninemia with severe neurological disorders, the 3,4-dihydroxyphenylalanine, i.e. DOPA, responsive form of dystonia, and endothelial dysfunction, all by (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin depletion, the GTP cyclohydrolase I feedback regulatory protein GFRP binds to the enzyme and mediates the regulation of the enzyme by L-phenylalanine and (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin Rattus norvegicus ?
-
 ?

Subunits

EC Number Subunits Comment Organism
3.5.4.16 decamer 2 pentamers which are positioned in a head-to-head manner to form the active decameric enzyme with an active site at the interface of each couple of dimer Rattus norvegicus
3.5.4.16 More stimulatory and inhibitory enzyme-GFRP-complex sandwich structure, subunit composition of GFRP pentamer is betabetaalphabetabetaalphabetabeta, overview Rattus norvegicus

Synonyms

EC Number Synonyms Comment Organism
3.5.4.16 GTPCHI
-
 Rattus norvegicus