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Literature summary for 3.5.4.16 extracted from

  • Li, L.; Rezvan, A.; Salerno, J.; Husain, A.; Kwon, K.; Jo, H.; Harrison, D.; Chen, W.
    GTP cyclohydrolase I phosphorylation and interaction with GTP cyclohydrolase feedback regulatory protein provide novel regulation of endothelial tetrahydrobiopterin and nitric oxide (2010), Circ. Res., 106, 328-336.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
additional information S81 phosphorylation enhances GTPCH-1 enzyme activity Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information S81D mutant produced significantly more NO than cells transfected with either wild type or S81A GTPCH-1 Homo sapiens
S81A site-directed mutagenesis, the mutant shows enhanced interaction with GFRP both in the presence of BH4 and GTP compared to the wild-type enzyme Homo sapiens
S81D site-directed mutagenesis, phospho-mimetic mutant that shows increased enzyme activity, reduced binding to GFRP, and resistance to inhibition by GFRP compared to wild-type GTPCH-1 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
GTP cyclohydrolase feedback regulatory protein i.e. GFRP, GTP cyclohydrolase I, GTPCH-1, undergoes negative feedback regulation by its endproduct tetrahydrobiopterin via interaction with the GTP cyclohydrolase feedback regulatory protein, GFRP. GFRP binding increased the apparent Km of GTPCH-1, which also contributes to inhibition and increases the cooperativity of substrate binding in the wild-type but not the S81D mutant. GFRP both inhibits and stimulates GTPCH-1 activity in vitro depending on interactions with either tetrahydrobiopterin or phenylalanine. GTPCH-1 phosphorylation reduces its binding to GFRP Homo sapiens
tetrahydrobiopterin GTP cyclohydrolase I, GTPCH-1, undergoes negative feedback regulation by its endproduct tetrahydrobiopterin via interaction with the GTP cyclohydrolase feedback regulatory protein, GFRP Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein S81 phosphorylation enhances GTPCH-1 enzyme activity, GFRP modulates phosphorylation of GTPCH-1, and GTPCH-1 phosphorylation reduces its binding to GFRP, overview Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
aortic endothelial cell
-
Homo sapiens
-
endothelium
-
Homo sapiens
-
lung
-
Homo sapiens
-

Synonyms

Synonyms Comment Organism
GTPCH-1
-
Homo sapiens

General Information

General Information Comment Organism
metabolism GTP cyclohydrolase I, GTPCH-1, is the rate-limiting enzyme involved in de novo biosynthesis of tetrahydrobiopterin, an essential cofactor for nitric oxide synthases and aromatic amino acid hydroxylases Homo sapiens
physiological function GTP cyclohydrolase I, GTPCH-1, is the rate-limiting enzyme involved in de novo biosynthesis of tetrahydrobiopterin, an essential cofactor for nitric oxide synthases and aromatic amino acid hydroxylases. GTPCH-1 undergoes negative feedback regulation by its endproduct tetrahydrobiopterin via interaction with the GTP cyclohydrolase feedback regulatory protein, GFRP. GTPCH-1 levels, GTPCH-1 phosphorylation status and GFRP levels play critical roles in regulating eNOS uncoupling in response to oscillatory shear stress, overview Homo sapiens