Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | S81 phosphorylation enhances GTPCH-1 enzyme activity | Homo sapiens |
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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
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 | Comment | Organism | Textmining |
---|---|---|---|
aortic endothelial cell | - |
Homo sapiens | - |
endothelium | - |
Homo sapiens | - |
lung | - |
Homo sapiens | - |
Synonyms | Comment | Organism |
---|---|---|
GTPCH-1 | - |
Homo sapiens |
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 |