The Mechanism of Potent GTP Cyclohydrolase I Inhibition by 2,4-Diamino-6-hydroxypyrimidine

Structure and mechanism of GTP cyclohydrolase I of Escherichia coli.

GTP cyclohydrolases I and I1 catalyze the first committed steps in the pathways of pteridine and flavin biosynthesis [ I ] . A reaction pathway for GTP cyclohydrolase I involving the release of C8 of GTP as formate, followed by Amadori rearrangement and ring closure (see Fig. I), has been proposed earlier [2]. The enzyme was first purified and characterised by Yim and Brown [3] Recombinant GTP ...

The Protein Partners of GTP Cyclohydrolase I in Rat Organs

OBJECTIVE GTP cyclohydrolase I (GCH1) is the rate-limiting enzyme for tetrahydrobiopterin biosynthesis and has been shown to be a promising therapeutic target in ischemic heart disease, hypertension, atherosclerosis and diabetes. The endogenous GCH1-interacting partners have not been identified. Here, we determined endogenous GCH1-interacting proteins in rat. METHODS AND RESULTS A pulldown an...

Defect in GTP-cyclohydrolase

Cloning and developmental expression of zebrafish GTP cyclohydrolase I

GTP cyclohydrolase I (GCH) catalyses the conversion of GTP to dihydroneopterin triphosphate, initiating the pteridine pathway. The final product tetrahydrobiopterin (H4biopterin) is the cofactor for neurotransmitter synthesis and for tyrosine supply during melanogenesis. Sepiapterin accumulates as a pigment. We cloned the zebrafish gch cDNA, which encodes a protein highly homologous to other ve...

Biochemical characterization of oligomerization of Escherichia coli GTP cyclohydrolase I.

GTP cyclohydrolase I (E.C. 3.5.4.16) is a homodecameric protein that catalyzes the conversion of GTP to 7,8- dihydroneopterin triphosphate (H(2)NTP), the initial step in the biosynthesis of pteridines. It was proposed that the enzyme complex could be composed of a dimer of two pentamers, or a pentamer of tightly associated dimers; then the active site of the enzyme was located at the interface ...