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Literature summary for 3.5.4.16 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

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

Crystallization (Commentary)

Crystallization (Comment) Organism
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

Inhibitors Comment Organism Structure
dihydrobiopterin induction of feedback inhibition, binding site structure Rattus norvegicus
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

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

Molecular Weight [Da]

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

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
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
-
?
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

Organism UniProt Comment Textmining
Rattus norvegicus
-
-
-

Reaction

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

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + H2O
-
Rattus norvegicus formate + 2-amino-4-hydroxy-6-(erythro-1,2,3-trihydroxypropyl)-dihydropteridine triphosphate
-
?
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
-
?
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

Subunits Comment Organism
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
More stimulatory and inhibitory enzyme-GFRP-complex sandwich structure, subunit composition of GFRP pentamer is betabetaalphabetabetaalphabetabeta, overview Rattus norvegicus

Synonyms

Synonyms Comment Organism
GTPCHI
-
Rattus norvegicus