| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| Structural basis of biopterin induced inhibition of GTP cyclohydrolase 1 by GFRP , its feedback regulatory protein . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| Purification and cloning of the GTP cyclohydrolase 1 feedback regulatory protein , GFRP . ^^^ This inhibition by tetrahydrobiopterin is mediated by the GTP cyclohydrolase 1 feedback regulatory protein GFRP , previously named p 35 ( Harada , T . , Kagamiyama , H . , and Hatakeyama , K . ( 1993 ) Science 260 , 1507 1510 ) , and phenylalanine specifically reverses the tetrahydrobiopterin dependent inhibition . ^^^ As a first step in the investigation of the physiological role of this unique mechanism of regulation , a convenient procedure has been developed to co purify to homogeneity both GTP cyclohydrolase 1 and GFRP from rat liver . ^^^ GTP cyclohydrolase 1 and GFRP exist in a complex which can be bound to a GTP affinity column from which GTP cyclohydrolase 1 and GFRP are separately and selectively eluted . ^^^ Both GFRP and GTP cyclohydrolase 1 were then purified separately to near homogeneity by sequential high performance anion exchange and gel filtration chromatography . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| GTP cyclohydrolase 1 feedback regulatory protein ( GFRP ) mediates feedback inhibition of GTP cyclohydrolase 1 activity by tetrahydrobiopterin and also mediates the stimulatory effect of phenylalanine on the enzyme activity . ^^^ Based on the pentameric structure of GFRP , we have proposed a model for the quaternary structure of GFRP and GTP cyclohydrolase 1 complexes . . ^^^ GTP cyclohydrolase 1 feedback regulatory protein is a pentamer of identical subunits . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| The activity of GTP cyclohydrolase 1 is inhibited by ( 6R ) L erythro 5 , 6 , 7 , 8 tetrahydrobiopterin ( BH 4 ) and stimulated by phenylalanine through complex formation with GTP cyclohydrolase 1 feedback regulatory protein ( GFRP ) . ^^^ Gel filtration experiments as well as enzyme activity measurements showed that the number of subunits of GFRP in both the inhibitory and stimulatory complexes is equal to that of GTP cyclohydrolase 1 . ^^^ Because GFRP is a pentamer and GTP cyclohydrolase 1 was shown here by cross linking experiments to be a decamer , the results indicate that two molecules of a pentameric GFRP associate with one molecule of GTP cyclohydrolase 1 . ^^^ These observations support our model that one molecule of GFRP binds to each of the two outer faces of the torus shaped GTP cyclohydrolase 1 . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| Mechanisms and unanticipated role of GTP cyclohydrolase 1 feedback regulatory protein . 2 , 4 Diamino 6 hydroxypyrimidine ( DAHP ) is considered to be a selective and direct acting inhibitor of GTP cyclohydrolase 1 ( GTPCH ) , the first and rate limiting enzyme in the pathway for synthesis of tetrahydrobiopterin ( BH 4 ) . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| Phenylalanine hydroxylase and 4a hydroxy 6BH4 dehydratase activities are significantly lower . mRNA of all enzymes involved in 6BH4 biosynthesis / recycling and GTP cyclohydrolase 1 feedback regulatory protein were expressed in keratinocytes from homozygotes , heterozygotes , and healthy controls . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| Tetrahydrobiopterin , the coenzyme required for hydroxylation of phenylalanine , tyrosine , and tryptophan , regulates its own synthesis through feedback inhibition of GTP cyclohydrolase 1 ( GTPCH ) mediated by a regulatory subunit , the GTP cyclohydrolase feedback regulatory protein ( GFRP ) . ^^^ GTP cyclohydrolase 1 feedback regulatory protein is expressed in serotonin neurons and regulates tetrahydrobiopterin biosynthesis . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| In the liver at least , activity is inhibited by BH ( 4 ) , but stimulated by phenylalanine through the GTP cyclohydrolase 1 feedback regulatory protein . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| GTP cyclohydrolase 1 feedback regulatory protein ( GFRP ) mediates feedback inhibition of GTP cyclohydrolase 1 activity by 6R L erythro 5 , 6 , 7 , 8 tetrahydrobiopterin ( BH 4 ) , which is an essential cofactor for key enzymes producing catecholamines , serotonin , and nitric oxide as well as phenylalanine hydroxylase . ^^^ GFRP also mediates feed forward stimulation of GTP cyclohydrolase 1 activity by phenylalanine at subsaturating GTP levels . ^^^ These ligands , BH 4 and phenylalanine , induce complex formation between one molecule of GTP cyclohydrolase 1 and two molecules of GFRP . ^^^ The binding stoichiometrics of BH 4 and phenylalanine were estimated to be 10 molecules of each per protein complex , in other words , one molecule per subunit of protein , because GTP cyclohydrolase 1 is a decamer and GFRP is a pentamer . ^^^ Regarding ligand binding to free proteins , BH 4 binds weakly to GTP cyclohydrolase 1 but not to GFRP , and phenylalanine binds weakly to GFRP but not to GTP cyclohydrolase 1 . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| GTP cyclohydrolase 1 feedback regulatory protein ( GFRP ) mediates the feedback inhibition of GTP cyclohydrolase 1 activity by ( 6R ) L erythro 5 , 6 , 7 , 8 tetrahydrobiopterin ( BH 4 ) through protein complex formation . ^^^ Guanine , 8 hydroxyguanine , 8 methylguanine , and 8 bromoguanine inhibited the enzyme activity in a GFRP dependent and pH dependent manner and induced complex formation between GTP cyclohydrolase 1 and GFRP . ^^^ GTP cyclohydrolase 1 feedback regulatory protein dependent and independent inhibitors of GTP cyclohydrolase 1 . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| Preparation and crystallization of the stimulatory and inhibitory complexes of GTP cyclohydrolase 1 and its feedback regulatory protein GFRP . ^^^ Here , both the stimulatory and inhibitory complexes of rat GTP cyclohydrolase 1 bound to GFRP were crystallized by vapour diffusion . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| Crystal structure of rat GTP cyclohydrolase 1 feedback regulatory protein , GFRP . ^^^ This mechanism is mediated by a regulatory subunit called GTP cyclohydrolase 1 feedback regulatory protein ( GFRP ) . ^^^ This indicates a model for the interaction of mammalian GTP cyclohydrolase 1 with its regulator , GFRP . ^^^ Kinetic investigations of human GTP cyclohydrolase 1 in complex with rat and human GFRP showed similar regulatory effects of both GFRP proteins . . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| GTP cyclohydrolase 1 feedback regulatory protein ( GFRP ) is a 9 . 7 kDa protein regulating GTP cyclohydrolase 1 activity in dependence of tetrahydrobiopterin and phenylalanine concentrations , thus enabling stimulation of tetrahydrobiopterin biosynthesis by phenylalanine to ensure its efficient metabolism by phenylalanine hydroxylase . ^^^ Here , we were interested in regulation of GFRP expression by proinflammatory cytokines and stimuli , which are known to induce GTP cyclohydrolase 1 expression . ^^^ Recombinant human GFRP stimulated recombinant human GTP cyclohydrolase 1 in the presence of phenylalanine and mediated feedback inhibition by tetrahydrobiopterin . ^^^ Levels of GFRP mRNA in human myelomonocytoma ( THP 1 ) cells remained unaltered by treatment of cells with interferon gamma or interleukin 1beta , but were significantly down regulated by bacterial lipopolysaccharide ( LPS , 1 microg / ml ) , without or with cotreatment by interferon gamma , which strongly up regulated GTP cyclohydrolase 1 expression and activity . ^^^ Bacterial lipopolysaccharide down regulates expression of GTP cyclohydrolase 1 feedback regulatory protein . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| Crystal structure of the stimulatory complex of GTP cyclohydrolase 1 and its feedback regulatory protein GFRP . ^^^ In the presence of phenylalanine , GTP cyclohydrolase 1 feedback regulatory protein ( GFRP ) forms a stimulatory 360 kDa complex with GTP cyclohydrolase 1 ( GTPCHI ) , which is the rate limiting enzyme in the biosynthesis of tetrahydrobiopterin . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| SNAP pretreatment suppressed the level of GTP cyclohydrolase 1 ( GTPCHI ) feedback regulatory protein ( GFRP ) and increased GTPCHI activity without changing GTPCHI protein level . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| This feedback inhibition is mediated through complex formation with the GTP cyclohydrolase 1 feedback regulatory protein ( GFRP ) . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| The mechanism of potent GTP cyclohydrolase 1 inhibition by 2 , 4 diamino 6 hydroxypyrimidine : requirement of the GTP cyclohydrolase 1 feedback regulatory protein . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| The activity of GTP cyclohydrolase 1 ( GTPCH 1 ) , the first enzyme in BH 4 biosynthesis , is controlled by protein levels , posttranslational modifications and interaction with GTPCH 1 feedback regulatory protein ( GFRP ) . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| We examined the effect of H ( 2 ) O ( 2 ) on the expression of GTP cyclohydrolase 1 ( GTPCH ) feedback regulating protein ( GFRP ) . ^^^ |
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| Interacting proteins: P30793 and P30047 |
Pubmed |
SVM Score :0.0 |
| The yeast 2 hybrid system was used to identify protein domains involved in the oligomerization of human guanosine 5 ' triphosphate ( GTP ) Cyclohydrolase 1 ( GCH 1 ) and the interaction of GCH 1 with its regulatory partner , GCH 1 feedback regulatory protein ( GFRP ) . ^^^ Moreover , a previously unknown role of the extended N terminal alpha helix in the interaction of GCH 1 and GFRP was revealed . ^^^ |
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