PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33229582-5 2020 GFRP binds to GCH1 to form inhibited or activated complexes dependent on availability of cofactor ligands, BH4 and phenylalanine, respectively. Phenylalanine 115-128 GTP cyclohydrolase 1 Homo sapiens 14-18 33387654-5 2021 Dependent on the relative cellular concentrations of effector ligands, BH4 and phenylalanine, GFRP binds GCH1 to form inhibited or activated complexes, respectively. Phenylalanine 79-92 GTP cyclohydrolase 1 Homo sapiens 105-109 33387654-8 2021 Further, analysis of all structures shows that upon binding of the effector molecules, the conformations of GCH1 or GFRP are altered and form highly complementary surfaces triggering a picomolar interaction of GFRP and GCH1 with extremely slow koff values, while GCH1-GFRP complexes rapidly disintegrate in absence of BH4 or phenylalanine. Phenylalanine 325-338 GTP cyclohydrolase 1 Homo sapiens 108-112 33387654-8 2021 Further, analysis of all structures shows that upon binding of the effector molecules, the conformations of GCH1 or GFRP are altered and form highly complementary surfaces triggering a picomolar interaction of GFRP and GCH1 with extremely slow koff values, while GCH1-GFRP complexes rapidly disintegrate in absence of BH4 or phenylalanine. Phenylalanine 325-338 GTP cyclohydrolase 1 Homo sapiens 219-223 33387654-8 2021 Further, analysis of all structures shows that upon binding of the effector molecules, the conformations of GCH1 or GFRP are altered and form highly complementary surfaces triggering a picomolar interaction of GFRP and GCH1 with extremely slow koff values, while GCH1-GFRP complexes rapidly disintegrate in absence of BH4 or phenylalanine. Phenylalanine 325-338 GTP cyclohydrolase 1 Homo sapiens 219-223 26014146-14 2015 In vivo, data demonstrated that L-phe elevated vascular BH4 in an endothelial GCH1 dependent manner. Phenylalanine 32-37 GTP cyclohydrolase 1 Homo sapiens 78-82 26014146-7 2015 We investigated the effects of L-phe on the biophysical interactions of GCH1 and GFRP and its potential to alter BH4 levels in vivo. Phenylalanine 31-36 GTP cyclohydrolase 1 Homo sapiens 72-76 26014146-10 2015 KEY RESULTS: GCH1 and GFRP proteins interacted in the absence of known ligands or substrate but the presence of L-phe doubled maximal binding and enhanced binding affinity eightfold. Phenylalanine 112-117 GTP cyclohydrolase 1 Homo sapiens 13-17 26014146-15 2015 Pharmacological agents which mimic the allosteric effects of L-phe on the GCH1-GFRP complex have the potential to elevate endothelial BH4 biosynthesis for numerous cardiovascular disorders. Phenylalanine 61-66 GTP cyclohydrolase 1 Homo sapiens 74-78 16778797-2 2006 The rate-limiting step of 6BH4 de novo synthesis is controlled by guanosine triphosphate (GTP) cyclohydrolase I (GTPCHI) and its feedback regulatory protein (GFRP), where binding of L-phenylalanine to GFRP increases enzyme activities, while 6BH4 exerts the opposite effect. Phenylalanine 182-197 GTP cyclohydrolase 1 Homo sapiens 66-111 22633640-5 2012 A phenylalanine loading test, cerebrospinal fluid for biogenic amines and pterins, guanosine triphosphate cyclohydrolase I enzyme activity, and direct exonic sequencing of GCH1 revealed a novel mutation (c.235_240delCTGAGC [p.L79_S80del]) in the GCH1 gene. Phenylalanine 2-15 GTP cyclohydrolase 1 Homo sapiens 172-176 21163945-3 2011 Subsequent phenylalanine binding to the GTPCH GFRP inhibitory complex converts it to a stimulatory complex. Phenylalanine 11-24 GTP cyclohydrolase 1 Homo sapiens 40-45 15946242-4 2005 We have previously showed that the overexpression of PAH and GTP cyclohydrolase I (GTP-CH), the rate-limiting enzyme in the synthesis of the cofactor for PAH, leads to high levels of phenylalanine clearance in primary human keratinocytes. Phenylalanine 183-196 GTP cyclohydrolase 1 Homo sapiens 61-81 15946242-4 2005 We have previously showed that the overexpression of PAH and GTP cyclohydrolase I (GTP-CH), the rate-limiting enzyme in the synthesis of the cofactor for PAH, leads to high levels of phenylalanine clearance in primary human keratinocytes. Phenylalanine 183-196 GTP cyclohydrolase 1 Homo sapiens 83-89 15448133-2 2004 In animals, the GTPCHI feedback regulatory protein (GFRP) binds GTPCHI to mediate feed-forward activation of GTPCHI activity in the presence of phenylalanine, whereas it induces feedback inhibition of enzyme activity in the presence of biopterin. Phenylalanine 144-157 GTP cyclohydrolase 1 Homo sapiens 16-22 15448133-2 2004 In animals, the GTPCHI feedback regulatory protein (GFRP) binds GTPCHI to mediate feed-forward activation of GTPCHI activity in the presence of phenylalanine, whereas it induces feedback inhibition of enzyme activity in the presence of biopterin. Phenylalanine 144-157 GTP cyclohydrolase 1 Homo sapiens 64-70 15448133-3 2004 Here, we have reported the crystal structure of the biopterin-induced inhibitory complex of GTPCHI and GFRP and compared it with the previously reported phenylalanine-induced stimulatory complex. Phenylalanine 153-166 GTP cyclohydrolase 1 Homo sapiens 92-98 15292175-7 2004 We further demonstrate that L-Phe fully reverses the inhibition of GTPCH by DAHP/GFRP, which is also a feature in common with inhibition by BH4/GFRP. Phenylalanine 28-33 GTP cyclohydrolase 1 Homo sapiens 67-72 11799107-1 2002 GTP cyclohydrolase I feedback regulatory protein (GFRP) is a 9.7-kDa protein regulating GTP cyclohydrolase I activity in dependence of tetrahydrobiopterin and phenylalanine concentrations, thus enabling stimulation of tetrahydrobiopterin biosynthesis by phenylalanine to ensure its efficient metabolism by phenylalanine hydroxylase. Phenylalanine 159-172 GTP cyclohydrolase 1 Homo sapiens 0-20 12208136-4 2002 We have previously shown that overexpression of PAH and GTP-CH in primary human keratinocytes leads to high levels of phenylalanine clearance without BH(4) supplementation [Gene Ther. Phenylalanine 118-131 GTP cyclohydrolase 1 Homo sapiens 56-62 12208136-7 2002 After retroviral gene transfer of PAH and GTP-CH both normal and PKU patient fibroblasts were able to metabolize phenylalanine, however, in lower amounts compared to genetically modified keratinocytes. Phenylalanine 113-126 GTP cyclohydrolase 1 Homo sapiens 42-48 12607127-5 2003 Furthermore, we looked for the influence of phenylalanine that is known to reverse BH(4)-mediated feedback inhibition of GTPCH I, and of immunostimulation with interferon gamma on the expression of GTPCH I and GFRP. Phenylalanine 44-57 GTP cyclohydrolase 1 Homo sapiens 121-128 12607127-12 2003 Phenylalanine stimulates the biosynthesis of BH(4) not only by reversing the negative feedback inhibition of GTPCH I but also by increasing the mRNA level of GTPCH I. Phenylalanine 0-13 GTP cyclohydrolase 1 Homo sapiens 109-116 12607127-12 2003 Phenylalanine stimulates the biosynthesis of BH(4) not only by reversing the negative feedback inhibition of GTPCH I but also by increasing the mRNA level of GTPCH I. Phenylalanine 0-13 GTP cyclohydrolase 1 Homo sapiens 158-165 11799107-1 2002 GTP cyclohydrolase I feedback regulatory protein (GFRP) is a 9.7-kDa protein regulating GTP cyclohydrolase I activity in dependence of tetrahydrobiopterin and phenylalanine concentrations, thus enabling stimulation of tetrahydrobiopterin biosynthesis by phenylalanine to ensure its efficient metabolism by phenylalanine hydroxylase. Phenylalanine 254-267 GTP cyclohydrolase 1 Homo sapiens 0-20 11799107-3 2002 Recombinant human GFRP stimulated recombinant human GTP cyclohydrolase I in the presence of phenylalanine and mediated feedback inhibition by tetrahydrobiopterin. Phenylalanine 92-105 GTP cyclohydrolase 1 Homo sapiens 52-72 11818540-1 2002 In the presence of phenylalanine, GTP cyclohydrolase I feedback regulatory protein (GFRP) forms a stimulatory 360-kDa complex with GTP cyclohydrolase I (GTPCHI), which is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. Phenylalanine 19-32 GTP cyclohydrolase 1 Homo sapiens 34-54 11818540-1 2002 In the presence of phenylalanine, GTP cyclohydrolase I feedback regulatory protein (GFRP) forms a stimulatory 360-kDa complex with GTP cyclohydrolase I (GTPCHI), which is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. Phenylalanine 19-32 GTP cyclohydrolase 1 Homo sapiens 153-159 11818540-4 2002 Five phenylalanine molecules are buried inside each interface between GFRP and GTPCHI, thus enhancing the binding of these proteins. Phenylalanine 5-18 GTP cyclohydrolase 1 Homo sapiens 79-85 11818540-5 2002 The complex structure suggests that phenylalanine-induced GTPCHI x GFRP complex formation enhances GTPCHI activity by locking the enzyme in the active state. Phenylalanine 36-49 GTP cyclohydrolase 1 Homo sapiens 58-64 11818540-5 2002 The complex structure suggests that phenylalanine-induced GTPCHI x GFRP complex formation enhances GTPCHI activity by locking the enzyme in the active state. Phenylalanine 36-49 GTP cyclohydrolase 1 Homo sapiens 99-105 8502995-4 1993 Furthermore, the inhibition was specifically reversed by phenylalanine, and, in conjunction with p35, phenylalanine reduced the cooperativity of GTP cyclohydrolase I. Phenylalanine 57-70 GTP cyclohydrolase 1 Homo sapiens 145-165 11274478-2 2001 GFRP also mediates feed-forward stimulation of GTP cyclohydrolase I activity by phenylalanine at subsaturating GTP levels. Phenylalanine 80-93 GTP cyclohydrolase 1 Homo sapiens 47-67 11274478-3 2001 These ligands, BH4 and phenylalanine, induce complex formation between one molecule of GTP cyclohydrolase I and two molecules of GFRP. Phenylalanine 23-36 GTP cyclohydrolase 1 Homo sapiens 87-107 11274478-7 2001 The binding stoichiometrics of BH4 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 I is a decamer and GFRP is a pentamer. Phenylalanine 39-52 GTP cyclohydrolase 1 Homo sapiens 177-197 11175307-3 2000 Here we show that overexpression of the two enzymes PAH and GTP-CH in primary human keratinocytes leads to high levels of phenylalanine clearance without BH4 supplementation. Phenylalanine 122-135 GTP cyclohydrolase 1 Homo sapiens 60-66 11175307-5 2000 Phenylalanine clearance was measured ex vivo in primary human keratinocytes cotransduced with PAH and GTP-CH (more than 370 nmol/24 h/106 cells), a level exceeding that of a human liver cell line (HepG2 cells). Phenylalanine 0-13 GTP cyclohydrolase 1 Homo sapiens 102-108 11175307-7 2000 Transfer of the two genes into the same cell was not necessary, since cocultivation of cells transduced separately with PAH and GTP-CH also resulted in phenylalanine clearance. Phenylalanine 152-165 GTP cyclohydrolase 1 Homo sapiens 128-134 9685352-0 1998 Decameric GTP cyclohydrolase I forms complexes with two pentameric GTP cyclohydrolase I feedback regulatory proteins in the presence of phenylalanine or of a combination of tetrahydrobiopterin and GTP. Phenylalanine 136-149 GTP cyclohydrolase 1 Homo sapiens 10-30 9685352-0 1998 Decameric GTP cyclohydrolase I forms complexes with two pentameric GTP cyclohydrolase I feedback regulatory proteins in the presence of phenylalanine or of a combination of tetrahydrobiopterin and GTP. Phenylalanine 136-149 GTP cyclohydrolase 1 Homo sapiens 67-87 9685352-1 1998 The activity of GTP cyclohydrolase I is inhibited by (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) and stimulated by phenylalanine through complex formation with GTP cyclohydrolase I feedback regulatory protein (GFRP). Phenylalanine 120-133 GTP cyclohydrolase 1 Homo sapiens 16-36