tryptophan 5-monooxygenase, tetrameric; This model describes tryptophan 5-monooxygenase, a ...
3-438
0e+00
tryptophan 5-monooxygenase, tetrameric; This model describes tryptophan 5-monooxygenase, a member of the family of tetrameric, biopterin-dependent aromatic amino acid hydroxylases found in metazoans. It is closely related to tetrameric phenylalanine-4-hydroxylase and tyrosine 3-monooxygenase, and more distantly related to the monomeric phenylalanine-4-hydroxylase found in some Gram-negative bacteria. [Energy metabolism, Amino acids and amines]
The actual alignment was detected with superfamily member TIGR01270:
Pssm-ID: 130337 [Multi-domain] Cd Length: 464 Bit Score: 749.76 E-value: 0e+00
tryptophan 5-monooxygenase, tetrameric; This model describes tryptophan 5-monooxygenase, a ...
3-438
0e+00
tryptophan 5-monooxygenase, tetrameric; This model describes tryptophan 5-monooxygenase, a member of the family of tetrameric, biopterin-dependent aromatic amino acid hydroxylases found in metazoans. It is closely related to tetrameric phenylalanine-4-hydroxylase and tyrosine 3-monooxygenase, and more distantly related to the monomeric phenylalanine-4-hydroxylase found in some Gram-negative bacteria. [Energy metabolism, Amino acids and amines]
Pssm-ID: 130337 [Multi-domain] Cd Length: 464 Bit Score: 749.76 E-value: 0e+00
Eukaryotic tryptophan hydroxylase (TrpOH); a member of the biopterin-dependent aromatic amino ...
106-392
0e+00
Eukaryotic tryptophan hydroxylase (TrpOH); a member of the biopterin-dependent aromatic amino acid hydroxylase family of non-heme, iron(II)-dependent enzymes that also includes prokaryotic and eukaryotic phenylalanine-4-hydroxylase (PheOH) and eukaryotic tyrosine hydroxylase (TyrOH). TrpOH oxidizes L-tryptophan to 5-hydroxy-L-tryptophan, the rate-limiting step in the biosynthesis of serotonin (5-hydroxytryptamine), a widely distributed hormone and neurotransmitter.
Pssm-ID: 239462 Cd Length: 287 Bit Score: 623.36 E-value: 0e+00
tryptophan 5-monooxygenase, tetrameric; This model describes tryptophan 5-monooxygenase, a ...
3-438
0e+00
tryptophan 5-monooxygenase, tetrameric; This model describes tryptophan 5-monooxygenase, a member of the family of tetrameric, biopterin-dependent aromatic amino acid hydroxylases found in metazoans. It is closely related to tetrameric phenylalanine-4-hydroxylase and tyrosine 3-monooxygenase, and more distantly related to the monomeric phenylalanine-4-hydroxylase found in some Gram-negative bacteria. [Energy metabolism, Amino acids and amines]
Pssm-ID: 130337 [Multi-domain] Cd Length: 464 Bit Score: 749.76 E-value: 0e+00
Eukaryotic tryptophan hydroxylase (TrpOH); a member of the biopterin-dependent aromatic amino ...
106-392
0e+00
Eukaryotic tryptophan hydroxylase (TrpOH); a member of the biopterin-dependent aromatic amino acid hydroxylase family of non-heme, iron(II)-dependent enzymes that also includes prokaryotic and eukaryotic phenylalanine-4-hydroxylase (PheOH) and eukaryotic tyrosine hydroxylase (TyrOH). TrpOH oxidizes L-tryptophan to 5-hydroxy-L-tryptophan, the rate-limiting step in the biosynthesis of serotonin (5-hydroxytryptamine), a widely distributed hormone and neurotransmitter.
Pssm-ID: 239462 Cd Length: 287 Bit Score: 623.36 E-value: 0e+00
phenylalanine-4-hydroxylase, tetrameric form; This model describes the larger, tetrameric form ...
15-437
0e+00
phenylalanine-4-hydroxylase, tetrameric form; This model describes the larger, tetrameric form of phenylalanine-4-hydroxylase, as found in metazoans. The enzyme irreversibly converts phenylalanine to tryosine and is known to be the rate-limiting step in phenylalanine catabolism in some systems. It is closely related to metazoan tyrosine 3-monooxygenase and tryptophan 5-monoxygenase, and more distantly to monomeric phenylalanine-4-hydroxylases of some Gram-negative bacteria. The member of this family from Drosophila has been described as having both phenylalanine-4-hydroxylase and tryptophan 5-monoxygenase activity (. However, a Drosophila member of the tryptophan 5-monoxygenase clade has subsequently been discovered.
Pssm-ID: 130335 [Multi-domain] Cd Length: 436 Bit Score: 587.19 E-value: 0e+00
Eukaryotic phenylalanine-4-hydroxylase (eu_PheOH); a member of the biopterin-dependent ...
106-411
0e+00
Eukaryotic phenylalanine-4-hydroxylase (eu_PheOH); a member of the biopterin-dependent aromatic amino acid hydroxylase family of non-heme, iron(II)-dependent enzymes that also includes prokaryotic phenylalanine-4-hydroxylase (pro_PheOH), eukaryotic tyrosine hydroxylase (TyrOH) and eukaryotic tryptophan hydroxylase (TrpOH). PheOH catalyzes the first and rate-limiting step in the metabolism of the amino acid L-phenylalanine (L-Phe), the hydroxylation of L-Phe to L-tyrosine (L-Tyr). It uses (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) as the physiological electron donor. The catalytic activity of the tetrameric enzyme is tightly regulated by the binding of L-Phe and BH4 as well as by phosphorylation. Mutations in the human enzyme are linked to a severe variant of phenylketonuria.
Pssm-ID: 239463 Cd Length: 306 Bit Score: 552.05 E-value: 0e+00
Eukaryotic tyrosine hydroxylase (TyrOH); a member of the biopterin-dependent aromatic amino ...
107-404
1.59e-173
Eukaryotic tyrosine hydroxylase (TyrOH); a member of the biopterin-dependent aromatic amino acid hydroxylase family of non-heme, iron(II)-dependent enzymes that also includes prokaryotic and eukaryotic phenylalanine-4-hydroxylase (PheOH) and eukaryotic tryptophan hydroxylase (TrpOH). TyrOH catalyzes the conversion of tyrosine to L-dihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of the catecholamines dopamine, noradrenaline, and adrenaline.
Pssm-ID: 239461 Cd Length: 298 Bit Score: 488.10 E-value: 1.59e-173
tyrosine 3-monooxygenase, tetrameric; This model describes tyrosine 3-monooxygenase, a member ...
14-436
1.60e-159
tyrosine 3-monooxygenase, tetrameric; This model describes tyrosine 3-monooxygenase, a member of the family of tetrameric, biopterin-dependent aromatic amino acid hydroxylases found in metazoans. It is closely related to tetrameric phenylalanine-4-hydroxylase and tryptophan 5-monooxygenase, and more distantly related to the monomeric phenylalanine-4-hydroxylase found in some Gram-negative bacteria.
Pssm-ID: 130336 [Multi-domain] Cd Length: 457 Bit Score: 458.63 E-value: 1.60e-159
Biopterin-dependent aromatic amino acid hydroxylase; a family of non-heme, iron(II)-dependent ...
162-385
3.07e-136
Biopterin-dependent aromatic amino acid hydroxylase; a family of non-heme, iron(II)-dependent enzymes that includes prokaryotic and eukaryotic phenylalanine-4-hydroxylase (PheOH), eukaryotic tyrosine hydroxylase (TyrOH) and eukaryotic tryptophan hydroxylase (TrpOH). PheOH converts L-phenylalanine to L-tyrosine, an important step in phenylalanine catabolism and neurotransmitter biosynthesis, and is linked to a severe variant of phenylketonuria in humans. TyrOH and TrpOH are involved in the biosynthesis of catecholamine and serotonin, respectively. The eukaryotic enzymes are all homotetramers.
Pssm-ID: 238215 Cd Length: 221 Bit Score: 390.38 E-value: 3.07e-136
Prokaryotic phenylalanine-4-hydroxylase (pro_PheOH); a member of the biopterin-dependent ...
156-381
3.79e-62
Prokaryotic phenylalanine-4-hydroxylase (pro_PheOH); a member of the biopterin-dependent aromatic amino acid hydroxylase family of non-heme, iron(II)-dependent enzymes that also includes the eukaryotic proteins, phenylalanine-4-hydroxylase (eu_PheOH), tyrosine hydroxylase (TyrOH) and tryptophan hydroxylase (TrpOH). PheOH catalyzes the hydroxylation of L-Phe to L-tyrosine (L-Tyr). It uses (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) as the physiological electron donor.
Pssm-ID: 239464 Cd Length: 228 Bit Score: 200.96 E-value: 3.79e-62
phenylalanine-4-hydroxylase, monomeric form; This model describes the smaller, monomeric form ...
156-380
5.31e-45
phenylalanine-4-hydroxylase, monomeric form; This model describes the smaller, monomeric form of phenylalanine-4-hydroxylase, as found in a small number of Gram-negative bacteria. The enzyme irreversibly converts phenylalanine to tryosine and is known to be the rate-limiting step in phenylalanine catabolism in some systems. This family is of biopterin and metal-dependent hydroxylases is related to a family of longer, multimeric aromatic amino acid hydroxylases that have additional N-terminal regulatory sequences. These include tyrosine 3-monooxygenase, phenylalanine-4-hydroxylase, and tryptophan 5-monoxygenase. [Energy metabolism, Amino acids and amines]
Pssm-ID: 130334 Cd Length: 248 Bit Score: 156.95 E-value: 5.31e-45
ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, tryptophan ...
18-91
1.01e-27
ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, tryptophan hydroxylases (TPH), both peripheral (TPH1) and neuronal (TPH2) enzymes; ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, tryptophan hydroxylases (TPH), both peripheral (TPH1) and neuronal (TPH2) enzymes. TPH catalyses the hydroxylation of L-Trp to 5-hydroxytryptophan, the rate limiting step in the biosynthesis of 5-hydroxytryptamine (serotonin) and the first reaction in the synthesis of melatonin. Very little is known about the role of the ACT domain in TPH, which appears to be regulated by phosphorylation but not by its substrate or cofactor. Members of this CD belong to the superfamily of ACT regulatory domains.
Pssm-ID: 153201 [Multi-domain] Cd Length: 74 Bit Score: 105.14 E-value: 1.01e-27
ACT domain of the nonheme iron-dependent, aromatic amino acid hydroxylases (AAAH); ACT domain ...
18-91
8.87e-21
ACT domain of the nonheme iron-dependent, aromatic amino acid hydroxylases (AAAH); ACT domain of the nonheme iron-dependent, aromatic amino acid hydroxylases (AAAH): Phenylalanine hydroxylases (PAH), tyrosine hydroxylases (TH) and tryptophan hydroxylases (TPH), both peripheral (TPH1) and neuronal (TPH2) enzymes. This family of enzymes shares a common catalytic mechanism, in which dioxygen is used by an active site containing a single, reduced iron atom to hydroxylate an unactivated aromatic substrate, concomitant with a two-electron oxidation of tetrahydropterin (BH4) cofactor to its quinonoid dihydropterin form. PAH catalyzes the hydroxylation of L-Phe to L-Tyr, the first step in the catabolic degradation of L-Phe; TH catalyses the hydroxylation of L-Tyr to 3,4-dihydroxyphenylalanine, the rate limiting step in the biosynthesis of catecholamines; and TPH catalyses the hydroxylation of L-Trp to 5-hydroxytryptophan, the rate limiting step in the biosynthesis of 5-hydroxytryptamine (serotonin) and the first reaction in the synthesis of melatonin. Eukaryotic AAAHs have an N-terminal ACT (regulatory) domain, a middle catalytic domain and a C-terminal domain which is responsible for the oligomeric state of the enzyme forming a domain-swapped tetrameric coiled-coil. The PAH, TH, and TPH enzymes contain highly conserved catalytic domains but distinct N-terminal ACT domains (this CD) and differ in their mechanisms of regulation. One commonality is that all three eukaryotic enzymes are regulated in part by the phosphorylation of serine residues N-terminal of the ACT domain. Members of this CD belong to the superfamily of ACT regulatory domains.
Pssm-ID: 153176 [Multi-domain] Cd Length: 74 Bit Score: 85.69 E-value: 8.87e-21
ACT domain of the nonheme iron-dependent, aromatic amino acid hydroxylases (AAAH); ACT domain ...
19-89
8.78e-14
ACT domain of the nonheme iron-dependent, aromatic amino acid hydroxylases (AAAH); ACT domain of the nonheme iron-dependent, aromatic amino acid hydroxylases (AAAH): Phenylalanine hydroxylases (PAH), tyrosine hydroxylases (TH) and tryptophan hydroxylases (TPH), both peripheral (TPH1) and neuronal (TPH2) enzymes. This family of enzymes shares a common catalytic mechanism, in which dioxygen is used by an active site containing a single, reduced iron atom to hydroxylate an unactivated aromatic substrate, concomitant with a two-electron oxidation of tetrahydropterin (BH4) cofactor to its quinonoid dihydropterin form. Eukaryotic AAAHs have an N-terminal ACT (regulatory) domain, a middle catalytic domain and a C-terminal domain which is responsible for the oligomeric state of the enzyme forming a domain-swapped tetrameric coiled-coil. The PAH, TH, and TPH enzymes contain highly conserved catalytic domains but distinct N-terminal ACT domains and differ in their mechanisms of regulation. One commonality is that all three eukaryotic enzymes appear to be regulated, in part, by the phosphorylation of serine residues N-terminal of the ACT domain. Also included in this CD are the C-terminal ACT domains of the bifunctional chorismate mutase-prephenate dehydratase (CM-PDT) enzyme and the prephenate dehydratase (PDT) enzyme found in plants, fungi, bacteria, and archaea. The P-protein of Escherichia coli (CM-PDT) catalyzes the conversion of chorismate to prephenate and then the decarboxylation and dehydration to form phenylpyruvate. These are the first two steps in the biosynthesis of L-Phe and L-Tyr via the shikimate pathway in microorganisms and plants. The E. coli P-protein (CM-PDT) has three domains with an N-terminal domain with chorismate mutase activity, a middle domain with prephenate dehydratase activity, and an ACT regulatory C-terminal domain. The prephenate dehydratase enzyme has a PDT and ACT domain. The ACT domain is essential to bring about the negative allosteric regulation by L-Phe binding. L-Phe binds with positive cooperativity; with this binding, there is a shift in the protein to less active tetrameric and higher oligomeric forms from a more active dimeric form. Members of this CD belong to the superfamily of ACT regulatory domains.
Pssm-ID: 153152 [Multi-domain] Cd Length: 75 Bit Score: 65.98 E-value: 8.78e-14
ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, phenylalanine ...
2-82
9.57e-13
ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, phenylalanine hydroxylases (PAH); ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, phenylalanine hydroxylases (PAH). PAH catalyzes the hydroxylation of L-Phe to L-Tyr, the first step in the catabolic degradation of L-Phe. In PAH, an autoregulatory sequence, N-terminal of the ACT domain, extends across the catalytic domain active site and regulates the enzyme by intrasteric regulation. It appears that the activation by L-Phe induces a conformational change that converts the enzyme to a high-affinity and high-activity state. Modulation of activity is achieved through inhibition by BH4 and activation by phosphorylation of serine residues of the autoregulatory region. The molecular basis for the cooperative activation process is not fully understood yet. Members of this CD belong to the superfamily of ACT regulatory domains.
Pssm-ID: 153203 [Multi-domain] Cd Length: 90 Bit Score: 63.68 E-value: 9.57e-13
ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, tyrosine ...
18-74
1.97e-07
ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, tyrosine hydroxylases (TH); ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, tyrosine hydroxylases (TH). TH catalyses the hydroxylation of L-Tyr to 3,4-dihydroxyphenylalanine, the rate limiting step in the biosynthesis of catecholamines (dopamine, noradrenaline and adrenaline), functioning as hormones and neurotransmitters. The enzyme is not regulated by its amino acid substrate, but instead by phosphorylation at several serine residues located N-terminal of the ACT domain, and by feedback inhibition by catecholamines at the active site. Members of this CD belong to the superfamily of ACT regulatory domains.
Pssm-ID: 153202 [Multi-domain] Cd Length: 115 Bit Score: 49.32 E-value: 1.97e-07
Prephenate dehydratase [Amino acid transport and metabolism]; Prephenate dehydratase is part ...
2-89
4.98e-06
Prephenate dehydratase [Amino acid transport and metabolism]; Prephenate dehydratase is part of the Pathway/BioSystem: Aromatic amino acid biosynthesis
Pssm-ID: 439847 [Multi-domain] Cd Length: 274 Bit Score: 47.79 E-value: 4.98e-06
C-terminal ACT domain of the bifunctional chorismate mutase-prephenate dehydratase (CM-PDT) ...
18-89
1.15e-04
C-terminal ACT domain of the bifunctional chorismate mutase-prephenate dehydratase (CM-PDT) enzyme and the prephenate dehydratase (PDT) enzyme; The C-terminal ACT domain of the bifunctional chorismate mutase-prephenate dehydratase (CM-PDT) enzyme and the prephenate dehydratase (PDT) enzyme, found in plants, fungi, bacteria, and archaea. The P-protein of E. coli (CM-PDT, PheA) catalyzes the conversion of chorismate to prephenate and then the decarboxylation and dehydration to form phenylpyruvate. These are the first two steps in the biosynthesis of L-Phe and L-Tyr via the shikimate pathway in microorganisms and plants. The E. coli P-protein (CM-PDT) has three domains with an N-terminal domain with chorismate mutase activity, a middle domain with prephenate dehydratase activity, and an ACT regulatory C-terminal domain. The prephenate dehydratase enzyme has a PDT and ACT domain. The ACT domain is essential to bring about the negative allosteric regulation by L-Phe binding. L-Phe binds with positive cooperativity; with this binding, there is a shift in the protein to less active tetrameric and higher oligomeric forms from a more active dimeric form. Members of this CD belong to the superfamily of ACT regulatory domains.
Pssm-ID: 153177 [Multi-domain] Cd Length: 80 Bit Score: 40.56 E-value: 1.15e-04
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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