Tunnelling fold (T-fold) family protein such as dihydroneopterin-triphosphate epimerase (DHNTPE), dihydroneopterin aldolase (DHNA) , GTP cyclohydrolase I (GTPCH-1), 6-pyrovoyl tetrahydropterin synthetase (PTPS), and uricase (UO,uroate/urate oxidase)
Tunnelling fold (T-fold). The five known T-folds are found in five different enzymes with ...
40-220
1.08e-102
Tunnelling fold (T-fold). The five known T-folds are found in five different enzymes with different functions: dihydroneopterin-triphosphate epimerase (DHNTPE), dihydroneopterin aldolase (DHNA) , GTP cyclohydrolase I (GTPCH-1), 6-pyrovoyl tetrahydropterin synthetase (PTPS), and uricase (UO,uroate/urate oxidase). They bind to substrates belonging to the purine or pterin families, and share a fold-related binding site with a glutamate or glutamine residue anchoring the substrate and a lot of conserved interactions. They also share a similar oligomerization mode: several T-folds join together to form a beta(2n)alpha(n) barrel, then two barrels join together in a head-to-head fashion to made up the native enzymes. The functional enzyme is a tetramer for UO, a hexamer for PTPS, an octamer for DHNA/DHNTPE and a decamer for GTPCH-1. The substrate is located in a deep and narrow pocket at the interface between monomers. In PTPS, the active site is located at the interface of three monomers, two from one trimer and one from the other trimer. In GTPCH-1, it is also located at the interface of three subunits, two from one pentamer and one from the other pentamer. There are four equivalent active sites in UO, six in PTPS, eight in DHNA/DHNTPE and ten in GTPCH-1. Each globular multimeric enzyme encloses a tunnel which is lined with charged residues for DHNA and UO, and with basic residues in PTPS. The N and C-terminal ends are located on one side of the T-fold while the residues involved in the catalytic activity are located at the opposite side. In PTPS, UO and DHNA/DHNTPE, the N and C-terminal extremities of the enzyme are located on the exterior side of the functional multimeric enzyme. In GTPCH-1, the extra C-terminal helix places the extremity inside the tunnel.
The actual alignment was detected with superfamily member TIGR00063:
Pssm-ID: 469697 [Multi-domain] Cd Length: 180 Bit Score: 294.74 E-value: 1.08e-102
GTP cyclohydrolase I; alternate names: Punch (Drosophila),GTP cyclohydrolase I (EC 3.5.4.16) catalyzes the biosynthesis of formic acid and dihydroneopterin triphosphate from GTP. This reaction is the first step in the biosynthesis of tetrahydrofolate in prokaryotes, of tetrahydrobiopterin in vertebrates, and of pteridine-containing pigments in insects. [Biosynthesis of cofactors, prosthetic groups, and carriers, Folic acid]
Pssm-ID: 129173 [Multi-domain] Cd Length: 180 Bit Score: 294.74 E-value: 1.08e-102
GTP cyclohydrolase I (GTP-CH-I) catalyzes the conversion of GTP into dihydroneopterin ...
35-220
1.07e-93
GTP cyclohydrolase I (GTP-CH-I) catalyzes the conversion of GTP into dihydroneopterin triphosphate. The enzyme product is the precursor of tetrahydrofolate in eubacteria, fungi, and plants and of the folate analogs in methanogenic bacteria. In vertebrates and insects it is the biosynthtic precursor of tetrahydrobiopterin (BH4) which is involved in the formation of catacholamines, nitric oxide, and the stimulation of T lymphocytes. The biosynthetic reaction of BH4 is controlled by a regulatory protein GFRP which mediates feedback inhibition of GTP-CH-I by BH4. This inhibition is reversed by phenylalanine. The decameric GTP-CH-I forms a complex with two pentameric GFRP in the presence of phenylalanine or a combination of GTP and BH4, respectively.
Pssm-ID: 238349 [Multi-domain] Cd Length: 185 Bit Score: 271.95 E-value: 1.07e-93
GTP cyclohydrolase I; alternate names: Punch (Drosophila),GTP cyclohydrolase I (EC 3.5.4.16) catalyzes the biosynthesis of formic acid and dihydroneopterin triphosphate from GTP. This reaction is the first step in the biosynthesis of tetrahydrofolate in prokaryotes, of tetrahydrobiopterin in vertebrates, and of pteridine-containing pigments in insects. [Biosynthesis of cofactors, prosthetic groups, and carriers, Folic acid]
Pssm-ID: 129173 [Multi-domain] Cd Length: 180 Bit Score: 294.74 E-value: 1.08e-102
GTP cyclohydrolase I (GTP-CH-I) catalyzes the conversion of GTP into dihydroneopterin ...
35-220
1.07e-93
GTP cyclohydrolase I (GTP-CH-I) catalyzes the conversion of GTP into dihydroneopterin triphosphate. The enzyme product is the precursor of tetrahydrofolate in eubacteria, fungi, and plants and of the folate analogs in methanogenic bacteria. In vertebrates and insects it is the biosynthtic precursor of tetrahydrobiopterin (BH4) which is involved in the formation of catacholamines, nitric oxide, and the stimulation of T lymphocytes. The biosynthetic reaction of BH4 is controlled by a regulatory protein GFRP which mediates feedback inhibition of GTP-CH-I by BH4. This inhibition is reversed by phenylalanine. The decameric GTP-CH-I forms a complex with two pentameric GFRP in the presence of phenylalanine or a combination of GTP and BH4, respectively.
Pssm-ID: 238349 [Multi-domain] Cd Length: 185 Bit Score: 271.95 E-value: 1.07e-93
Tunnelling fold (T-fold). The five known T-folds are found in five different enzymes with ...
97-190
1.91e-08
Tunnelling fold (T-fold). The five known T-folds are found in five different enzymes with different functions: dihydroneopterin-triphosphate epimerase (DHNTPE), dihydroneopterin aldolase (DHNA) , GTP cyclohydrolase I (GTPCH-1), 6-pyrovoyl tetrahydropterin synthetase (PTPS), and uricase (UO,uroate/urate oxidase). They bind to substrates belonging to the purine or pterin families, and share a fold-related binding site with a glutamate or glutamine residue anchoring the substrate and a lot of conserved interactions. They also share a similar oligomerization mode: several T-folds join together to form a beta(2n)alpha(n) barrel, then two barrels join together in a head-to-head fashion to made up the native enzymes. The functional enzyme is a tetramer for UO, a hexamer for PTPS, an octamer for DHNA/DHNTPE and a decamer for GTPCH-1. The substrate is located in a deep and narrow pocket at the interface between monomers. In PTPS, the active site is located at the interface of three monomers, two from one trimer and one from the other trimer. In GTPCH-1, it is also located at the interface of three subunits, two from one pentamer and one from the other pentamer. There are four equivalent active sites in UO, six in PTPS, eight in DHNA/DHNTPE and ten in GTPCH-1. Each globular multimeric enzyme encloses a tunnel which is lined with charged residues for DHNA and UO, and with basic residues in PTPS. The N and C-terminal ends are located on one side of the T-fold while the residues involved in the catalytic activity are located at the opposite side. In PTPS, UO and DHNA/DHNTPE, the N and C-terminal extremities of the enzyme are located on the exterior side of the functional multimeric enzyme. In GTPCH-1, the extra C-terminal helix places the extremity inside the tunnel.
Pssm-ID: 238351 Cd Length: 122 Bit Score: 50.91 E-value: 1.91e-08
Database: CDSEARCH/cdd Low complexity filter: no Composition Based Adjustment: yes E-value threshold: 0.01
References:
Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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