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Information on EC 1.14.16.1 - phenylalanine 4-monooxygenase and Organism(s) Homo sapiens and UniProt Accession P00439

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IUBMB Comments
The active centre contains mononuclear iron(II). The reaction involves an arene oxide that rearranges to give the phenolic hydroxy group. This results in the hydrogen at C-4 migrating to C-3 and in part being retained. This process is known as the NIH-shift. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
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Homo sapiens
UNIPROT: P00439
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
phenylalanine hydroxylase, phenylalanine 4-monooxygenase, pheoh, phenylalanine 4-hydroxylase, phenylalanine monooxygenase, dicpah, cepah, l-phenylalanine 4-hydroxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phenylalanine monooxygenase
-
oxygenase, phenylalanine 4-mono-
-
-
-
-
phenylalaninase
-
-
-
-
phenylalanine 4-hydroxylase
-
-
-
-
phenylalanine hydroxylase
PheOH
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-phenylalanine + a 5,6,7,8-tetrahydropteridine + O2 = L-tyrosine + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
show the reaction diagram
L-phenylalanine + a 5,6,7,8-tetrahydropteridine + O2 = L-tyrosine + a 4a-hydroxy-5,6,7,8-tetrahydropteridine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxygenation
S-oxygenation
oxidation
-
redox reaction
-
-
-
-
oxidation
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
L-phenylalanine,tetrahydrobiopterin:oxygen oxidoreductase (4-hydroxylating)
The active centre contains mononuclear iron(II). The reaction involves an arene oxide that rearranges to give the phenolic hydroxy group. This results in the hydrogen at C-4 migrating to C-3 and in part being retained. This process is known as the NIH-shift. The 4a-hydroxytetrahydropteridine formed can dehydrate to 6,7-dihydropteridine, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydropteridine must be enzymically reduced back to tetrahydropteridine, by EC 1.5.1.34, 6,7-dihydropteridine reductase, before it slowly rearranges into the more stable but inactive compound 7,8-dihydropteridine.
CAS REGISTRY NUMBER
COMMENTARY hide
9029-73-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(S)-butyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
low activity
-
-
?
(S)-carboxymethyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
(S)-carboxymethyl-L-cysteine S-oxide + dihydrobiopterin + H2O
show the reaction diagram
low activity
-
-
?
(S)-ethyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
(S)-ethyl-L-cysteine S-oxide + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
?
(S)-ethyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
low activity
-
-
?
(S)-methyl-ergothionine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
low activity
-
-
?
(S)-methyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
(S)-methyl-L-cysteine S-oxide + dihydrobiopterin + H2O
show the reaction diagram
low activity
-
-
?
(S)-propyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
low activity
-
-
?
3-(2-thienyl)-L-alanine + tetrahydrobiopterin + O2
? + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
?
L-methionine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
low activity
-
-
?
L-norleucine + tetrahydrobiopterin + O2
? + dihydrobiopterin + H2O
show the reaction diagram
5% of the activity with 3-(2-thienyl)-L-alanine
-
-
?
L-phenylalanine + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxy-(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
show the reaction diagram
L-phenylalanine + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
?
L-phenylalanine + (7R,S)-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
r
L-phenylalanine + 5,6,7,8-tetrahydro-L-biopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
?
L-phenylalanine + 5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
L-phenylalanine + 6-methyl-tetrahydrobiopterin + O2
L-tyrosine + 6-methyl-4a-hydroxy-tetrahydrobiopterin
show the reaction diagram
-
-
-
?
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxy-tetrahydrobiopterin
show the reaction diagram
-
-
-
?
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
?
N-acetyl-(S)-carboxymethyl-L-cysteine + 5,6,7,8-tetrahydro-L-biopterin + O2
N-acetyl-(S)-carboxymethyl-L-cysteine S-oxide + ?
show the reaction diagram
-
-
-
?
N-acetyl-(S)-carboxymethyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
?
N-acetyl-(S)-methyl-L-cysteine + 5,6,7,8-tetrahydro-L-biopterin + O2
N-acetyl-(S)-methyl-L-cysteine S-oxide + ?
show the reaction diagram
-
-
-
?
N-acetyl-(S)-methyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
?
N-acetyl-S-carboxymethyl-L-cysteine + O2
?
show the reaction diagram
-
-
-
?
N-acetyl-S-methyl-L-cysteine + O2
?
show the reaction diagram
-
-
-
?
S-carboxymethyl-L-cysteine + 5,6,7,8-tetrahydro-L-biopterin + O2
S-carboxymethyl-L-cysteine S-oxide + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
?
S-carboxymethyl-L-cysteine + tetrahydrobiopterin + O2
S-carboxymethyl-L-cysteine S-oxide + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
?
S-methyl-L-cysteine + O2
?
show the reaction diagram
-
-
-
?
3-(2-thienyl)-L-alanine + 6-methyltetrahydropterin + O2
? + 6-methyldihydropterin + H2O
show the reaction diagram
-
-
-
-
?
4-fluorophenylalanine + tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
Abz-VAA + tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
r
L-methionine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
L-Phe + tetrahydrobiopterin + O2
L-tyrosine + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
-
?
L-phenylalanine + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxy-(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
show the reaction diagram
L-phenylalanine + (7R)-5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
r
L-phenylalanine + 5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxy-tetrahydrobiopterin
show the reaction diagram
-
substrate binding by His285, Trp326, Arg270, Ser349, and Trp278
-
-
?
L-phenylalanine + 5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-phenylalanine + 6,7-dimethyltetrahydrobiopterin
L-tyrosine + 6,7-dimethyl-4a-hydroxy-tetrahydrobiopterin
show the reaction diagram
-
-
-
-
r
L-phenylalanine + 6-methyltetrahydropterin + O2
L-tyrosine + 4a-hydroxy-6-methyltetrahydropterin
show the reaction diagram
-
-
-
-
?
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxy-tetrahydrobiopterin
show the reaction diagram
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + dihydrobiopterin + H2O
show the reaction diagram
L-thienylalanine + tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
L-tryptophan + tetrahydrobiopterin + O2
?
show the reaction diagram
-
truncated enzyme containing C-terminal 334 amino acids
-
-
?
phenylalanine + tetrahydrobiopterin + O2
tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
PAH is a key enzyme in the metabolic pathway of phenylalanine. Deficiency in PAH leads to high and persistent levels of this amino acid in theplasma of phenylketonuria patients, causing permanent neurological damage
-
-
ir
S-carboxy-methyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
S-carboxymethyl-L-cysteine S-oxide + dihydrobiopterin + H2O
show the reaction diagram
-
poor substrate
-
-
?
S-carboxymethyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
S-carboxymethyl-L-cysteine S-oxide + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
-
?
S-carboxymethyl-L-cysteine + tetrahydrobiopterin + O2
?
show the reaction diagram
-
conversion to the (S)-sulfoxide
-
-
?
S-carboxymethyl-L-cysteine + tetrahydrobiopterin + O2
S-carboxymethyl-L-cysteine S-oxide + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
-
?
S-methyl-ergothionine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
S-methyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
S-methyl-L-cysteine S-oxide + dihydrobiopterin + H2O
show the reaction diagram
-
poor substrate
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-phenylalanine + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxy-(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
show the reaction diagram
-
-
-
?
L-phenylalanine + 5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
?
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxy-tetrahydrobiopterin
show the reaction diagram
-
-
-
?
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxy-tetrahydrobiopterin
show the reaction diagram
L-phenylalanine + tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
phenylalanine + tetrahydrobiopterin + O2
tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
PAH is a key enzyme in the metabolic pathway of phenylalanine. Deficiency in PAH leads to high and persistent levels of this amino acid in theplasma of phenylketonuria patients, causing permanent neurological damage
-
-
ir
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
(7R)-tetrahydrobiopterin
8fold lower affinity and activity compared with 6(R)BH4
(7S)-tetrahydrobiopterin
8fold lower affinity and activity compared with 6(R)BH4
5,6,7,8-tetrahydro-L-biopterin
6-methyl-tetrahydrobiopterin
-
tetrahydrobiopterin
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
-
5,6,7,8-tetrahydro-L-biopterin
-
-
tetrahydrobiopterin
additional information
cofactor binding analysis, overview
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
contains one Fe2+ per monomer
Cl-
-
bound by residue S391
Iron
-
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(7R)-tetrahydrobiopterin
slight inhibition, synthetic pathway, overview, conformational structure by NMR
(7S)-tetrahydrobiopterin
strong, competitive inhibition, synthetic pathway, overview, conformational structure by NMR
5,6-dimethyl-3-(4-methyl-2-pyridinyl)-2-thioxo-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-one
weak competitive inhibitor
7(S)-tetrahydrobiopterin
-
(7R)-5,6,7,8-tetrahydrobiopterin
-
-
(7R)-5,6,7,8-tetrahydropterin
-
0.001 mM, 50% inhibition at 0.5 mM phenylalanine, 0.004 mM, 50% inhibition at 0.1 mM phenylalanine, recombinant enzyme
2,2'-dipyridyl
-
99.0% inhibition at 1.0 mM using L-phenylalanine as substrate, 99.0% inhibition at 1.0 mM using S-carboxymethyl-L-cysteine as substrate
3-iodotyrosine
-
3.0% inhibition at 1.0 mM using L-phenylalanine as substrate, 5.2% inhibition at 1.0 mM using S-carboxymethyl-L-cysteine as substrate
4-chloromercuribenzoate
-
1 mM, complete inhibition after 10 min
4-Chlorophenylalanine
4-Fluorophenylalanine
-
above 1 mM
6-Fluorotryptophan
-
2.5% inhibition at 1.0 mM using L-phenylalanine as substrate, 4.5% inhibition at 1.0 mM using S-carboxymethyl-L-cysteine as substrate
copper-chelating agents
-
-
-
diethyldithiocarbamate
-
1 mM, 58% inhibition
DL-alpha-tocopherol
-
strong inhibition
Iron-chelating agents
-
-
-
L-methionine
-
competitive inhibitor of the C-oxidation of L-phenylalanine
L-phenylalanine
-
competitive inhibition of the S-oxidation of S-carboxymethyl-L-cysteine, 92.8% inhibition at 1.0 mM using S-carboxymethyl-L-cysteine as substrate
S-carboxy-methyl-L-cysteine
-
competitive inhibitor of the C-oxidation of L-phenylalanine
S-carboxymethyl-L-cysteine
-
competitive inhibitor of the aromatic C-oxidation of L-phenylalanine, 25.2% inhibition at 5.0 mM using L-phenylalanine as substrate
S-methyl-ergothionine
-
competitive inhibitor of the C-oxidation of L-phenylalanine
S-methyl-L-cysteine
-
competitive inhibitor of the C-oxidation of L-phenylalanine
tetrahydrobiopterin
-
excessive dosages of BH4 inhibit PAH under normal phenylalanine conditions in vivo and activate PAH under conditions of high phenylalanine, overview
Thiol-binding reagents
-
-
-
tryptophan
-
recombinant enzyme, 3 mM, approx. 75% inhibition
tyrosine
-
recombinant enzyme, 3 mM, approx. 50% inhibition
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
glycerol
does no affect the wild-type enzyme activity at 1-5%, but increases the activity of the mutant enzymes about 1-3fold, overview
L-phenylalanine
cAMP-dependent protein kinase
-
H2O2
-
2 mM, up to 4fold increase in activity, mixed activation mechanism, oxidation of Trp120 to 5-hydroxy-Trp120
lysolecithin
phenylalanine
Phospholipids
-
activate
tetrahydrobiopterin
-
excessive dosages of BH4 inhibit PAH under normal phenylalanine conditions in vivo and activate PAH under conditions of high phenylalanine, overview
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.027 - 0.053
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
8.3
(S)-carboxymethyl-L-cysteine
wild type enzyme, in 50 mM potassium phosphate buffer, pH 6.8, at 37°C
20.3
(S)-methyl-L-cysteine
wild type enzyme, in 50 mM potassium phosphate buffer, pH 6.8, at 37°C
0.022 - 0.155
5,6,7,8-tetrahydrobiopterin
0.22
7(R,S)-tetrahydrobiopterin
pH 7.0, 25°C, recombinant enzyme
0.022 - 1.1
L-phenylalanine
29.8
N-acetyl-(S)-carboxymethyl-L-cysteine
wild type enzyme, in 50 mM potassium phosphate buffer, pH 6.8, at 37°C
32.1
N-acetyl-(S)-methyl-L-cysteine
wild type enzyme, in 50 mM potassium phosphate buffer, pH 6.8, at 37°C
57.15 - 63.8
N-acetyl-S-carboxymethyl-L-cysteine
60.54 - 68.25
N-acetyl-S-methyl-L-cysteine
0.0728 - 25.24
S-carboxymethyl-L-cysteine
44.63 - 51.6
S-methyl-L-cysteine
0.032 - 0.047
tetrahydrobiopterin
0.003 - 0.025
(6R)-5,6,7,8-tetrahydrobiopterin
0.008 - 0.024
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
0.2
(7R)-5,6,7,8-tetrahydrobiopterin
-
recombinant enzyme
1
4-Fluorophenylalanine
-
approx. value
0.0231 - 0.07812
5,6,7,8-tetrahydrobiopterin
0.033
6,7-dimethyltetrahydropterin
-
-
0.01 - 0.1
6-methyltetrahydropterin
0.008 - 0.028
Abz-VAA
3.1
L-methionine
-
at 37°C, 50 mM potassium phosphate buffer, pH 6.8
0.1 - 3
L-Phe
0.05 - 7.14
L-phenylalanine
0.043 - 0.55
phenylalanine
4.6
S-carboxy-methyl-L-cysteine
-
at 37°C, 50 mM potassium phosphate buffer, pH 6.8
2 - 25.24
S-carboxymethyl-L-cysteine
0.3
S-methyl-ergothionine
-
at 37°C, 50 mM potassium phosphate buffer, pH 6.8
18.32
S-methyl-L-cysteine
-
at 37°C, 50 mM potassium phosphate buffer, pH 6.8
0.0026 - 0.082
tetrahydrobiopterin
0.024 - 0.096
tryptophan
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0183 - 6.58
phenylalanine
additional information
additional information
-
wild-type PAH kinetic analyses using a new assay reveal cooperativity of activated PAH toward (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0023 - 0.0049
7(S)-tetrahydrobiopterin
pH 7.0, 25°C, recombinant enzyme, versus (6R)-tetrahydrobiopterin
0.0015
(7R)-5,6,7,8-tetrahydrobiopterin
-
-
1.1
4-Chlorophenylalanine
-
-
3.5
L-methionine
-
at 37°C, 50 mM potassium phosphate buffer, pH 6.8
5.01
S-carboxy-methyl-L-cysteine
-
at 37°C, 50 mM potassium phosphate buffer, pH 6.8
17.23
S-carboxymethyl-L-cysteine
-
in pooled hepatic cytosolic enzyme fraction, at 37°C
0.41
S-methyl-ergothionine
-
at 37°C, 50 mM potassium phosphate buffer, pH 6.8
17.32
S-methyl-L-cysteine
-
at 37°C, 50 mM potassium phosphate buffer, pH 6.8
additional information
additional information
inhibition kinetics
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0009
mutant enzyme V388M, using S-carboxymethyl-L-cysteine as substrate
0.0014
0.0015
mutant enzyme Y414C, using S-carboxymethyl-L-cysteine as substrate
0.0016
mutant enzyme R261Q, using S-carboxymethyl-L-cysteine as substrate
0.0049
L-phenylalanine-activated mutant enzyme S231F, at 25°C
0.0052
non-L-phenylalanine-activated mutant enzyme S231F, at 25°C
0.073
wild type enzyme, using S-carboxymethyl-L-cysteine as substrate
0.099
R270K mutant enzyme, expression in the absence of glycerol in the growth medium, cofactor 6-methyltetrahydropterin
0.23
R270K mutant enzyme, expression in the presence of glycerol in the growth medium, cofactor 6-methyltetrahydropterin
0.4169
non-L-phenylalanine-activated wild type enzyme, at 25°C
0.505
mutant enzyme V388M, using L-phenylalanine as substrate
0.7418
L-phenylalanine-activated wild type enzyme, at 25°C
0.75
mutant enzyme R408W, using L-phenylalanine as substrate, in 100 mM Na-HEPES buffer, pH 7.0, at 25°C
1.2
mutant enzyme Y414C, using L-phenylalanine as substrate
1.32
mutant enzyme R155H, using L-phenylalanine as substrate, in 100 mM Na-HEPES buffer, pH 7.0, at 25°C
1.49
mutant enzyme R261Q, using L-phenylalanine as substrate
1.64
mutant enzyme D143G, using L-phenylalanine as substrate, in 100 mM Na-HEPES buffer, pH 7.0, at 25°C
1.725
mutant enzyme R68S, using L-phenylalanine as substrate
1.773
V388M mutant enzyme, expression in the absence of glycerol in the growth medium, cofactor 6-methyltetrahydropterin
1.9
wild type enzyme, using L-phenylalanine as substrate
1.98
substrate L-phenylalanine, mutant N223D
2.25
mutant enzyme I65T, using L-phenylalanine as substrate
2.34
substrate tetrahydrobiopterin, mutant N223D
2.76
mutant enzyme L348V, using L-phenylalanine as substrate, in 100 mM Na-HEPES buffer, pH 7.0, at 25°C
2.84
substrate tetrahydrobiopterin, mutant T427P
2.91
V388M mutant enzyme, expression in the presence of glycerol in the growth medium, cofactor 6-methyltetrahydropterin
2.98
wild type enzyme, using L-phenylalanine as substrate, in 100 mM Na-HEPES buffer, pH 7.0, at 25°C
3.17
substrate L-phenylalanine, mutant T427P
3.32
mutant enzyme P416Q, using L-phenylalanine as substrate, in 100 mM Na-HEPES buffer, pH 7.0, at 25°C
3.48
substrate L-phenylalanine, wild-type
3.67
substrate L-phenylalanine, mutant N426D
3.74
substrate L-phenylalanine, mutant N32D
4.37
substrate L-phenylalanine, mutant G33A
4.39
substrate tetrahydrobiopterin, mutant N426D
5.16
substrate L-phenylalanine, mutant G33V
5.32
substrate tetrahydrobiopterin, wild-type
6.19
substrate L-phenylalanine, mutant K113P
6.41
substrate tetrahydrobiopterin, mutant G33V
8.56
substrate tetrahydrobiopterin, mutant K113P
0.055
-
I65T mutant enzyme, cofactor 6-methyltetrahydropterin
0.106
-
-
0.225
-
liver enzyme
0.408
-
V388M mutant enzyme, cofactor tetrahydrobiopterin
0.424
-
maltose-binding-protein phenylalanine hydroxylase fusion protein, dimeric form
0.536
-
R261Q mutant enzyme, cofactor tetrahydrobiopterin
0.745
-
V388M mutant enzyme, cofactor 6-methyltetrahydropterin
0.77
-
mutant R68V, preincubation with L-phenylalanine
0.78
-
R261Q mutant enzyme, cofactor 6-methyltetrahydropterin
1.08
-
mutant C237R
1.1
-
wild-type, preincubation with L-phenylalanine
1.13
-
mutant C237R, preincubation with L-phenylalanine
1.283
-
maltose-binding-protein phenylalanine hydroxylase fusion protein, tetrameric form
1.6
-
fetal liver enzyme
1.7
-
pH 7.0, 25°C, wild-type, dimer
1.742
-
recombinant wild-type enzyme, cofactor tetrahydrobiopterin
1.76
-
adult liver enzyme
1150
-
mutant Y325F, 25°C, pH 7.0
1230
-
wild-type, 25°C, pH 7.0
1310
-
mutant Y325L, 25°C, pH 7.0
14
-
truncated enzyme containing C-terminal 334 amino acids
1500
-
mutant Y325L, preincubation with L-phenylalanine, 25°C, pH 7.0
2.14
-
mutant R68V
2.2
-
mutant R68A, preincubation with L-phenylalanine
2.49
-
recombinant wild-type enzyme, cofactor 6-methyltetrahydropterin
2.6
-
recombinant enzyme
2.94
-
mutant R68A
2.97
-
mutant C237A
290
-
mutant Y325A, 25°C, pH 7.0
3.25
-
wild-type
3.81
-
mutant C237D
300
-
mutant Y325A, preincubation with L-phenylalanine, 25°C, pH 7.0
3630
-
mutant Y325F, preincubation with L-phenylalanine, 25°C, pH 7.0
3640
-
wild-type, preincubation with L-phenylalanine, 25°C, pH 7.0
4.19
-
mutant C237D, preincubation with L-phenylalanine
4.95
-
pH 7.0, 25°C, wild-type, tetramer
6.48
-
pH 7.0, 25°C, N-terminal deletion mutant
8.32
-
pH 7.0, 25°C, N-terminal plus C-terminal deletion mutant
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
6.8
-
assay at
7
-
assay at
7.3
-
assay at
7.8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 9.5
-
recombinant enzyme, 25% loss of activity at pH 5.5, 15% loss of activity at pH 7.0-8.0
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
assay at
25
-
assay at
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15 - 42
-
native and recombinant enzyme
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
key enzyme in the sulfoxidation of S-carboxymethyl-L-cysteine S-oxide and its thioester metabolites S-methyl-L-cysteine, N-acetyl-S-carboxymethyl-L-cysteine, and N-acetyl-S-methyl-L-cysteine
malfunction
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PH4H_HUMAN
452
0
51862
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
156000
gel filtration
26300
catalytic domain, calculated from amino acid sequence
50000
4 * 50000
52000
94000
approximately 94000 Da, SDS-PAGE
107000
-
fetal liver enzyme, sucrose density gradient centrifugation
110000
-
fetal liver enzyme, gel filtration
150000
-
adult liver enzyme, gel filtration
160000
-
fetal liver enzyme, gel filtration
165000
-
gel filtration
275000
-
-
49000
50000
-
4 * 50000, SDS-PAGE
52000
-
x * 52000 + x * 49000, fetal liver enzyme, SDS-PAGE
53000
-
x * 53000, recombinant enzyme, SDS-PAGE
54000
-
2 * 54000, fetal liver enzyme, SDS-PAGE
95600
-
calculated from amino acid sequence
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
homotetramer
oligomer
wild-type and mutant enzymes show different oligomeric states, from dimer to hexamer, overview
tetramer
dimer
homotetramer
-
-
tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
side-chain modification
additional information
-
self-hydroxylation mechanism at Phe325, dependent on iron at the active site
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of ternary complex of catalytic domain, Fe2+ form, with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine
in complex with 6(R)-L-erythro-5,6,7,8-tetrahydrobiopterin and substrate analogues 3-(2-thienyl)-L-alanine or L-norleucine
crystal structure of the catalytic domain in its catalytic active Fe2+ form and as binary complex with tetrahydrobiopterin, 1.7 and 1.5 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A202T
the mutation is associated with phenylketonuria
A259T
the mutation is associated with phenylketonuria
A300S
A313T
A403V
the mutation is associated with phenylketonuria
A447P
the mutation is associated with phenylketonuria
D143G
mutant with a mild misfolding defect associated with phenylketonuria
D338Y
the mutation is associated with phenylketonuria
E178G
E178G/Q232E
the mutant shows 55% activity compared to the wild type enzyme
E221G
the mutation is associated with phenylketonuria
E280K
the mutation is associated with phenylketonuria
E390G
E390G/R261Q
the mutant shows 63% activity compared to the wild type enzyme
E76A
the mutation is associated with phenylketonuria
F233I
inactive
F331S
the mutant shows residual enzymatic activity in vitro compared to the wild type enzyme
F382L
naturally occuring mutation and site-directed mutagenesis, the mutant shows 44% reduced activity compared to the wild-type enzyme, analysis of structural alterations
F39C
the mutant enzyme shows reduced activity compared to the wild type
F39L
the mutant enzyme shows reduced activity compared to the wild type
G247R
the mutation is associated with phenylketonuria
G332E
the mutation is associated with phenylketonuria
G33A
increased basal activity, reduced activation by preincubation with substrate
G33V
increased basal activity, reduced activation by preincubation with substrate
G344D
the mutation is associated with phenylketonuria
I174T
the mutation results in the classical phenylketonuria phenotype expressing 0.2-1.8% of the wild type PAH activity when using L-phenylalanine as substrate, and has less 0.1% of the wild type PAH activity when S-carboxymethyl-L-cysteine is used as the substrate
I224T
the mutation is associated with phenylketonuria
I306V
the mutation is associated with phenylketonuria
I65T/R261Q
the mutant shows 19.5% activity compared to the wild type enzyme
I65T/R408W
the mutant shows 15% activity compared to the wild type enzyme
I65V
the mutant enzyme shows reduced activity compared to the wild type
K113P
increased basal activity, reduced activation by preincubation with substrate, increase in positive cooperativity
K398K
naturally occuring mutation
K398N
naturally occuring mutation and site-directed mutagenesis, the mutant shows 45% reduced activity compared to the wild-type enzyme, analysis of structural alterations
L212P
the mutant shows about 20% activity compared to the wild type enzyme
L213P
the mutation is associated with phenylketonuria
L249F
L249P
L311P
the mutation is associated with phenylketonuria
L348V
L358F
the mutant shows residual enzymatic activity in vitro compared to the wild type enzyme
L48S/R261Q
the mutant shows 35% activity compared to the wild type enzyme
N223D
low basal activity, little activation by preincubation with substrate, increase in positive cooperativity
N223Y
naturally occuring mutation and site-directed mutagenesis, the mutant shows 30% reduced activity compared to the wild-type enzyme, analysis of structural alterations
N32D
low basal activity, close to normal activation by preincubation with substrate
N426D
low basal activity, close to normal activation by preincubation with substrate
P225T
the mutation is associated with phenylketonuria
P281L
P281S
the mutation is associated with phenylketonuria
P384S
the mutant shows 76% activity compared to the wild type enzyme
P384S/R408W
the mutant shows 56.1% activity compared to the wild type enzyme
P416Q
the mutant retains significant catalytic activity yet is observed in classic and moderate phenylketonuria patients
Q232E
the mutant shows 42% activity compared to the wild type enzyme
Q419R
naturally occuring mutation and site-directed mutagenesis, the mutant shows 29% reduced activity compared to the wild-type enzyme, analysis of structural alterations
R111X
the mutation is associated with phenylketonuria
R155H
the mutant displays low PAH activity and decreased apparent affinity for L-Phe yet is observed in mild hyperphenylalaninaemia, mutant does not display kinetic instability, as it is stabilized by (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin similarly to wild type enzyme
R158Q
R158Q/R261Q
the mutant shows 23% activity compared to the wild type enzyme
R158W
the mutation is associated with phenylketonuria
R176X
the mutation is associated with phenylketonuria
R241C
the mutation is associated with phenylketonuria
R241H
the mutation is associated with phenylketonuria
R243Q
R243X
exon 6 C727T mutation naturally occuring in phenylketonuria patients from the Cukurova region in Turkey, sequence determination and analysis
R252W
the mutation is associated with phenylketonuria
R261P
the mutant shows about 14% activity compared to the wild type enzyme
R261Q
R270I
inactive
R270K
R297C
naturally occuring mutation
R297H
naturally occuring mutation
R297L
naturally occuring mutation and site-directed mutagenesis, the mutant shows 58% reduced activity compared to the wild-type enzyme, analysis of structural alterations
R408Q
R408W
R408W/A300S
the mutant shows 18% activity compared to the wild type enzyme
R408W/I283F
the mutant shows 2% residual activity compared to the wild type enzyme
R408W/I306V
the mutant shows 18% residual activity compared to the wild type enzyme
R408W/P281L
inactive
R408W/pA403V
the mutant shows 20% residual activity compared to the wild type enzyme
R408W/R158Q
R408W/R261Q
the mutant shows 18% activity compared to the wild type enzyme
R408W/R297H
the mutant shows 15% residual activity compared to the wild type enzyme
R408W/R408W
inactive
R408W/Y414C
the mutant shows 40% activity compared to the wild type enzyme
R413P
the mutation is associated with phenylketonuria
S196Y
the mutant shows about 20% activity compared to the wild type enzyme
S231F
the missense phenylalanine hydroxylase gene mutation causes complete loss of enzymatic activity in vitro (residual enzyme activity in vitro is about 1%) as it drastically reduces stability and activity of the PAH enzyme, the mutant enzyme is not activated by pre-incubation with L-phenylalanine substrate
S310F
the mutation is associated with phenylketonuria
S348L
instable enzyme forming aggregates after expression in Escherichia coli in the presence of GroESL
S349A
the mutation is associated with phenylketonuria
S349P
the mutation is associated with phenylketonuria
S350Y
inactive
T278I
the mutation is associated with phenylketonuria
T380M
the mutant shows about 25% activity compared to the wild type enzyme
T427P
low basal activity, little activation by preincubation with substrate, no kinetic cooperativity
T63P
the mutation is associated with phenylketonuria
V245A
the mutant shows 50% activity compared to the wild type enzyme
V245A/R261Q
the mutant shows 55% activity compared to the wild type enzyme
V379D/H264Q
the mutant shows significant activity at tyrosine hydroxylation and a 3000fold decrease in preference for phenylalanine over tyrosine as the substrate
V388M
W187X
the mutation is associated with phenylketonuria
Y138A
the mutant shows reduced catalytic efficiency (about 38%) compared to the wild type enzyme
Y138E
the mutant shows reduced catalytic efficiency (about 15%) compared to the wild type enzyme
Y138F
the mutant shows reduced catalytic efficiency (about 55%) compared to the wild type enzyme
Y138K
the mutant shows severely reduced catalytic efficiency (about 5%) compared to the wild type enzyme
Y168H
the mutation is associated with phenylketonuria
Y204C
Y356X
the mutation is associated with phenylketonuria
Y386C
exon 11 A1157G mutation naturally occuring in phenylketonuria patient from the Cukurova region in Turkey, sequence determination and analysis
Y387H
the mutation is associated with phenylketonuria
Y414C
Y414C/R261Q
the mutant shows 64% activity compared to the wild type enzyme
A104D
A259T
-
the mutant with wild type activity exhibits less than 50% of wild type protein level
A259V
-
the mutant with wild type activity exhibits less than 50% of wild type protein level and leads to classic phenyletonuria
A300S
A309V
-
the mutant shows 70% of wild type activity
A322G
-
the mutant shows 75% of wild type activity
A395G
-
naturally occuring mutation involved in hyperphenylalaninemia and/or in phenylketonuria, overview
A403V
A434D
-
the mutation is associated with phenylketonuria
A447P
-
site-directed mutagenesis, the mutation occurs naturally in phenylketonuria patients from Korea, the mutant shows highly reduced activity compared to the wild-type
C237A
-
increase of basal activity and affinity for substrate L-phenylalanine
C237D
C237R
-
reduced activity, elimination of positive cooperativity
C237S
-
approx. 2fold higher activity than wild-type
D415N
-
naturally occuring missense mutation causing a mild phenylketonuria phenotype
DELTA1-102
-
mutant lacking the first 102 residues corresponding to the N-terminal regulatory domain. 96% of the truncated mutant exist as a tetramer. On coexpression of wild-type-hPAH and the N-terminally truncated form DELTA1-102 (~95% tetramer), heterotetramers, as a result of an assembly of two different homodimers, are isolated. The recovered (wild-type)/(DELTA1-102 mutant)-hPAH heterotetramers reveal a catalytic activity deviating significantly from that calculated by averaging the respective recombinant homotetrameric forms. The heterotetramer assembly also results in conformational changes in the WT-hPAH protomer, as detected by trypsin limited proteolysis
DELTA1-102/DELTAC24
-
mutant lacking the first 102 residues corresponding to the N-terminal regulatory domain and the last 24 residues at the C-terminal end corresponding to the tetramerisation motif. 81% of the truncated mutant exist as a dimer and 17% as an aggregated form. On co-expression of wild-type-hPAH (50% tetramer, 10% dimer) and the N- and C-terminally truncated form DELTA1-102/DELTAC24 (80% dimer) no heterodimers is recovered
DELTA103-427
-
dimeric double-truncated form: the dimeric variant 103-427 shows a Vmax (1980 nmol Tyr/min/mg protein) comparable with that of the non-activated wild-type PAH, which does not change markedly upon L-Phe preincubation (2421 nmol Tyr/min/mg protein)
E280G
-
the mutation is associated with phenylketonuria
E280K
F161S
F39L
-
the mutant has approximately 3fold higher specific activity than the wild type enzyme and leads to moderate phenyletonuria
F39L/F55fsdelT
-
naturally occuring mutation in the regulatory domain, that affects enzyme activity and causes an atypical form of phenylketonuria
F39L/P281L
-
naturally occuring mutation in the regulatory domain, that affects enzyme activity and causes the classical form of phenylketonuria
F39L/R408W
-
naturally occuring mutation in the regulatory domain, that affects enzyme activity and causes the classical form of phenylketonuria
G103S
-
site-directed mutagenesis, the mutation occurs naturally in phenylketonuria patients from Korea, the mutant shows highly reduced activity compared to the wild-type
G218V
-
the mutant shows wild type activity
G247V
G332V
-
site-directed mutagenesis, the mutation occurs naturally in phenylketonuria patients from Korea, inactive mutant
H271Q
-
naturally occuring knockout missense mutation leading to a severe phenylketonuria phenotype
I174T
-
heteromeric hPAH (wild-type + mutant) shows: significantly decreased Vmax values compared to wild-type, significantly increased Km values (substrate: S-carboxymethyl-L-cysteine or L-Phe) compared to wild-type
I174V
-
naturally occuring missense mutation causing a mild phenylketonuria phenotype
I65T/R408W
I65T/R68S
-
naturally occuring mutation in the regulatory domain, that affects enzyme activity and causes a mild form of phenylketonuria
I95F
-
naturally occuring missense mutation causing a mild phenylketonuria phenotype
I97L
-
naturally occuring mutation in the regulatory domain, that affects enzyme activity and is involved in the disorder hyperphenylalaninemia
K42I
-
the mutant shows 12% of wild type activity
L197F
-
naturally occuring knockout missense mutation leading to a severe phenylketonuria phenotype
L212P
naturally occuring mutation involved in phenylketonuria
L255S
L255V
-
the mutant shows 13% of wild type activity
L293M
-
site-directed mutagenesis, the mutation occurs naturally in phenylketonuria patients from Korea, the mutant shows reduced activity and no response to tetrahydrobiopterin compared to the wild-type
L311P
-
the mutant with wild type activity exhibits less than 50% of wild type protein level and leads to classic phenyletonuria
L348V
L41F
-
the mutant shows 10% of wild type activity
P122Q
-
the mutant with wild type activity exhibits less than 50% of wild type protein level
P225T
-
naturally occuring knockout missense mutation leading to a severe phenylketonuria phenotype
P244L
-
the mutant shows 68% of wild type activity
P281L
P366H
-
naturally occuring mutation involved in hyperphenylalaninemia and/or in phenylketonuria, overview
P69S
-
site-directed mutagenesis, the mutation occurs naturally in phenylketonuria patients from Korea, the mutant shows reduced activity compared to the wild-type
Q232X
-
the mutation is associated with phenylketonuria
R111X
-
the mutation is associated with phenylketonuria
R155H
-
the mutation is associated with phenylketonuria
R157N
-
the mutant with wild type activity exhibits less than 50% of wild type protein level
R158Q
R158W
-
naturally occuring mutation involved in hyperphenylalaninemia and/or in phenylketonuria, overview
R176X
-
the mutation is associated with phenylketonuria
R241C
-
site-directed mutagenesis, the mutation occurs naturally in humans altering the tetrahydrobiopterin responsiveness, the mutant shows reduced activity and dimer stability compared to the wild-type
R243Q
R252G
-
the mutant with wild type activity exhibits less than 50% of wild type protein level and leads to classic phenyletonuria
R252Q
-
the mutant with wild type activity exhibits less than 50% of wild type protein level and leads to classic phenyletonuria
R252W
R261P
-
naturally occuring missense mutation causing a mild phenylketonuria phenotype
R261Q
R270S
-
the mutant shows 3% of wild type activity
R313P
-
the mutation is associated with phenylketonuria
R408Q
R408W
R413P
R53H
-
site-directed mutagenesis, the mutation occurs naturally in humans altering the tetrahydrobiopterin responsiveness, the mutant shows reduced activity and dimer stability compared to the wild-type
R68A
-
increase of basal activity and affinity for substrate L-phenylalanine
R68G
-
the mutant shows wild type activity
R68S/R408W
-
naturally occuring mutation in the regulatory domain, that affects enzyme activity and causes an atypical form of phenylketonuria
R68V
-
little decrease in activity
R71C
-
naturally occuring mutation in the regulatory domain, that affects enzyme activity and is involved in the disorder hyperphenylalaninemia
R86S
-
for the variants R68S and V106A, a Vmax comparable with the activated wild-type PAH is found without L-Phe preincubation, and no further increase is measured when the substrate is present. R68S and V106A without L-Phe preincubation show lower cofactor affinities than the non-activated wild-type PAH. Values are at the same level as determined for the L-Phe preincubated wild-type PAH
S349L
-
inactive
S349P
S391I
-
site-directed mutagenesis, the mutation occurs naturally in phenylketonuria patients from Korea, inactive mutant
T427P
-
increase in the amount of oligomeric forms higher than tetramers after preincubation of a mixture of dimeric and tetrameric forms with phenylalanine, tetrameric form exhibits approx. 50% of wild-type tetramer phenylalanine hydroxylase activity
V106A
-
for the variants R68S and V106A, a Vmax comparable with the activated wild-type PAH is found without L-Phe preincubation, and no further increase is measured when the substrate is present. R68S and V106A without L-Phe preincubation show lower cofactor affinities than the non-activated wild-type PAH. Values are at the same level as determined for the L-Phe preincubated wild-type PAH
V388M
Y166X
-
the mutation is associated with phenylketonuria
Y277D
-
inactive
Y325A
Y325F
Y325L
-
stable, similar yields and oligomeric distribution as wild-type, reduced specific activity, decreased coupling efficiency and decreased iron content, no positive cooperativity for L-phenylalanine
Y325S
-
aggregation after purification, not suitable for characterization
Y356X
-
the mutation is associated with phenylketonuria
Y414C
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50
V388M mutant enzyme, 50% activity after 10 min
51
L348V mutant enzyme, 50% activity after 10 min
59
recombinant wild-type enzyme, 50% activity after 10 min
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
phenylalanine stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, enzyme concentration 1 mg/ml, several months, no loss of activity
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
amylose column chromatography
double truncated mutant enzyme DELTAN1-102/DELTAC428-452
recombinant His6-tagged wild-type and mutant enzymes from Escherichia coli by nickel affinity chromatography
recombinant His6-tagged, catalytically active, heterozygous enzymes with one mutated allele, from bacteria by nickel affinity chromatography, excision of the His-tag
recombinant wild-type, L348V and V388M mutant enzyme, affinity chromatography
recombinant wild-type, R270K and V388M mutant enzymes expressed in the presence and absence of glycerol
Superdex 200 gel filtration
adult and fetal liver enzyme, monoclonal antibody affinity chromatography
-
ammonium sulfate, Phenyl-Sepharose, DEAE-Sepharose, recombinant enzyme
-
fetal, newborn and adult enzyme are probably identical
-
HiTrap Q column chromatography
-
Phenyl-Sepharose, DEAE-Sepharose
-
recombinant enzyme, partially purified
-
recombinant His-tagged enzyme in fusion with HIV transactivator of transcription protein from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type, I65T, R261Q and V388M mutant enzymes, affinity chromatography
-
recombinant maltose-binding-protein phenylalanine hydroxylase fusion protein
-
recombinant wild-type enzyme and deletion mutants
-
truncated enzyme containing the C-terminal 343 amino acids
-
using Ni-NTA chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence analysis of wild-type and mutant enzymes, expression of His6-tagged, catalytically active, heterozygous enzymes with one mutated allele
DNA and amino acid sequence determination and analysis of wild-type and mutant enzymes, overview
DNA and amino acid sequence determination and analysis, genotyping, expression of mutant enzymes in HEK-193 cells
expressed in COS-7 cells
expressed in Escherichia coli as fusion proteins with maltose-binding protein
expressed in Escherichia coli TB1 cells
expressed in Hep-G2 cells
expressed in Lactobacillus plantarum strain CM PUJ411
expression of double truncated mutant enzyme DELTAN1-102/DELTAC428-452 in Escherichia coli
expression of wild-type, L348V, L349L and V388M mutant enzyme maltose-binding-protein fusions in Escherichia coli and COS cells
expression of wild-type, R270K and V388M mutant enzymes in the presence of the chemical chaperone glycerol
gene pah, expression of His6-tagged wild-type and mutant enzymes in Escherichia coli
mutant enzymes are expressed in Escherichia coli
the catalytic domain is expressed in Escherichia coli BL21(DE3) cells
wild type and mutant enzyme S231F are expressed in Escherichia coli BL21(DE3) and human hepatoma cells, in the cells supplemented with sepiapterin the amount of expressed S231F PAH increases up to 25%
expressed in Escherichia coli
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expressed in Escherichia coli as a recombinant protein
-
expression as maltose-binding-protein fusion protein in Escherichia coli circumvents proteolytic degradation by the host cell
-
expression in Escherichia coli
-
expression of His-tagged wild-type, I65T, R261Q and V388M mutant enzymes in Escherichia coli
-
expression of wild-type and T427P mutant enzyme in Escherichia coli
-
expression of wild-type enzyme and Asp112-Lys452, Ser2-Gln428 and Gly103-Gln428 deletion mutants in Escherichia coli
-
gene pah, DNA and amino acid sequence determination and analysis, genotyping of a Southern Italian population, overview
-
gene pah, DNA and amino acid sequence determination and analysis, genotyping, overview
-
gene pah, DNA and amino acid sequence determination of wild-type and mutant enzymes, genotyping
-
gene pah, expression of His-tagged enzyme in fusion with HIV transactivator of transcription protein in Escherichia coli strain BL21(DE3), subcloning in Escherichi acoli strain DH5alpha
-
gene PHA, DNA sequence determination, structural and functional analyses of mutations of the PHA gene, expression of wild-type and mutant enzymes in COS-7 cells, overview
-
identification and sequence analysis of enzyme mutant genes with exon deletions isolated from 59 czech phenylketonuria patients, multiplex ligation-dependent probe amplification method
-
truncated enzyme containing the C-terminal 336 amino acids bearing the catalytic domain
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
molecular biology
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kaufman, S.
Aromatic amino acid hydroxylases
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
18
217-282
1987
Homo sapiens, Rattus norvegicus
-
Manually annotated by BRENDA team
Abita, J.P.; Blandin-Savoja, F.; Rey, F.
Phenylalanine 4-monooxygenase from human liver
Methods Enzymol.
142
27-35
1987
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Yamashita, M.; Minato, S.; Arai, M.; Kishida, Y.; Nagatsu, T.; Umezawa, H.
Purification of phenylalanine hydroxylase from human adult and foetal livers with a monoclonal antibody
Biochem. Biophys. Res. Commun.
133
202-207
1985
Homo sapiens
Manually annotated by BRENDA team
Ledley, F.D.; Grenett, H.E.; Woo, S.L.C.
Biochemical characterization of recombinant human phenylalanine hydroxylase produced in Escherichia coli
J. Biol. Chem.
262
2228-2233
1987
Homo sapiens
Manually annotated by BRENDA team
Woo, S.L.C.; Gillam, S.S.; Woolf, L.I.
The isolation and properties of phenylalanine hydroxylase from human liver
Biochem. J.
139
741-749
1974
Homo sapiens
Manually annotated by BRENDA team
Martinez, A.; Knappskog, P.M.; Olafsdottir, S.; Doskeland, A.P.; Eiken, H.G.; Svebak, R.M.; Bozzini, M.; Apold, J.; Flatmark, T.
Expression of recombinant human phenylalanine hydroxylase as fusion protein in Escherichia coli circumvents proteolytic degradation by host cell proteases. Isolation and characterization of the wild-type enzyme
Biochem. J.
306
589-597
1995
Homo sapiens
-
Manually annotated by BRENDA team
Doeskeland, A.P.; Martinez, A.; Knappskog, P.M.; Flatmark, T.
Phosphorylation of recombinant human phenylalanine hydroxylase: effect on catalytic activity, substrate activation and protection against non-specific cleavage of the fusion protein by restriction protease
Biochem. J.
313
409-414
1996
Homo sapiens
-
Manually annotated by BRENDA team
Kowlessur, D.; Citron, B.A.; Kaufman, S.
Recombinant human phenylalanine hydroxylase: novel regulatory and structural properties
Arch. Biochem. Biophys.
333
85-95
1996
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Knappskog, P.M.; Flatmark, T.; Aarden, J.M.; Haavik, J.; Martinez, A.
Structure/function relationships in human phenylalanine hydroxylase. Effect of terminal deletions on the oligomerization, activation and cooperativity of substrate binding to the enzyme
Eur. J. Biochem.
242
813-821
1996
Homo sapiens
Manually annotated by BRENDA team
Knappskog, P.M.; Martinez, A.
Effect of mutations at Cys237 on the activation state and activity of human phenylalanine hydroxylase
FEBS Lett.
409
7-11
1997
Homo sapiens
Manually annotated by BRENDA team
Daubner, S.C.; Hillas, P.J.; Fitzpatrick, P.F.
Expression and characterization of the catalytic domain of human phenylalanine hydroxylase
Arch. Biochem. Biophys.
348
295-302
1997
Homo sapiens
Manually annotated by BRENDA team
Teigen, K.; Froystein, N.A.; Martinez, A.
The structural basis of the recognition of phenylalanine and pterin cofactors by phenylalanine hydroxylase: implications for the catalytic mechanism
J. Mol. Biol.
294
807-823
1999
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Gamez, A.; Perez, B.; Ugarte, M.; Desviat, L.R.
Expression analysis of phenylketonuria mutations: effect on folding and stability of the phenylalanine hydroxylase protein
J. Biol. Chem.
275
29737-29742
2000
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Leandro, P.; Rivera, I.; Lechner, M.C.; de Almeida, I.T.; Konecki, D.
The V388M mutation results in a kinetic variant form of phenylalanine hydroxylase
Mol. Genet. Metab.
69
204-212
2000
Homo sapiens
Manually annotated by BRENDA team
Andersen, O.A.; Flatmark, T.; Hough, E.
High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin
J. Mol. Biol.
314
279-291
2001
Homo sapiens
Manually annotated by BRENDA team
Leandro, P.; Lechner, M.C.; Tavares de Almeida, I.; Konecki, D.
Glycerol increases the yield and activity of human phenylalanine hydroxylase mutant enzymes produced in a prokaryotic expression system
Mol. Genet. Metab.
73
173-178
2001
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Bjorgo, E.; De Carvalho, R.M.N.; Flatmark, T.
A comparison of kinetic and regulatory properties of the tetrameric and dimeric forms of wild-type and Thr427->Pro mutant human phenylalanine hydroxylase. Contribution of the flexible hinge region Asp425-Gln429 to the tetramerization and cooperative substrate binding
Eur. J. Biochem.
268
997-1005
2001
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Andreas Andersen, O.; Flatmark, T.; Hough, E.
Crystal structure of the ternary complex of the catalytic domain of human phenylalanine hydroxylase with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine, and its implications for the mechanism of catalysis and substrate activation
J. Mol. Biol.
320
1095-1108
2002
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Erlandsen, H.; Kim, J.Y.; Patch, M.G.; Han, A.; Volner, A.; Abu-Omar, M.M.; Stevens, R.C.
Structural comparison of bacterial and human iron-dependent phenylalanine hydroxylases: similar fold, different stability and reaction rates
J. Mol. Biol.
320
645-661
2002
Homo sapiens (P00439), Homo sapiens, Chromobacterium violaceum (P30967), Chromobacterium violaceum
Manually annotated by BRENDA team
Schallreuter, K.U.; Wazir, U.; Kothari, S.; Gibbons, N.C.; Moore, J.; Wood, J.M.
Human phenylalanine hydroxylase is activated by H2O2: a novel mechanism for increasing the L-tyrosine supply for melanogenesis in melanocytes
Biochem. Biophys. Res. Commun.
322
88-92
2004
Homo sapiens
Manually annotated by BRENDA team
Stokka, A.J.; Flatmark, T.
Substrate-induced conformational transition in human phenylalanine hydroxylase as studied by surface plasmon resonance analyses: the effect of terminal deletions, substrate analogues and phosphorylation
Biochem. J.
369
509-518
2003
Homo sapiens
Manually annotated by BRENDA team
Thorolfsson, M.; Teigen, K.; Martinez, A.
Activation of phenylalanine hydroxylase: effect of substitutions at Arg68 and Cys237
Biochemistry
42
3419-3428
2003
Homo sapiens
Manually annotated by BRENDA team
Kinzie, S.D.; Thevis, M.; Ngo, K.; Whitelegge, J.; Loo, J.A.; Abu-Omar, M.M.
Posttranslational hydroxylation of human phenylalanine hydroxylase is a novel example of enzyme self-repair within the second coordination sphere of catalytic iron
J. Am. Chem. Soc.
125
4710-4711
2003
Homo sapiens
Manually annotated by BRENDA team
Stokka, A.J.; Carvalho, R.N.; Barroso, J.F.; Flatmark, T.
Probing the role of crystallographically defined/predicted hinge-bending regions in the substrate-induced global conformational transition and catalytic activation of human phenylalanine hydroxylase by single-site mutagenesis
J. Biol. Chem.
279
26571-26580
2004
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Miranda, F.F.; Kolberg, M.; Andersson, K.K.; Geraldes, C.F.; Martinez, A.
The active site residue tyrosine 325 influences iron binding and coupling efficiency in human phenylalanine hydroxylase
J. Inorg. Biochem.
99
1320-1328
2005
Homo sapiens
Manually annotated by BRENDA team
Andersen, O.A.; Stokka, A.J.; Flatmark, T.; Hough, E.
2.0A resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine or L-norleucine: substrate specificity and molecular motions related to substrate binding
J. Mol. Biol.
333
747-757
2003
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Pey, A.L.; Martinez, A.
The activity of wild-type and mutant phenylalanine hydroxylase and its regulation by phenylalanine and tetrahydrobiopterin at physiological and pathological concentrations: An isothermal titration calorimetry study
Mol. Genet. Metab.
86
S43-53
2005
Homo sapiens
Manually annotated by BRENDA team
Leandro, J.; Nascimento, C.; Tavares de Almeida, I.; Leandro, P.
Co-expression of different subunits of human phenylalanine hydroxylase: Evidence of negative interallelic complementation
Biochim. Biophys. Acta
1762
544-550
2006
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Kim, S.W.; Jung, J.; Oh, H.J.; Kim, J.; Lee, K.S.; Lee, D.H.; Park, C.; Kimm, K.; Koo, S.K.; Jung, S.C.
Structural and functional analyses of mutations of the human phenylalanine hydroxylase gene
Clin. Chim. Acta
365
279-287
2006
Homo sapiens
Manually annotated by BRENDA team
Boonyapiwat, B.; Panagopoulos, P.; Jones, H.; Mitchell, S.C.; Forbes, B.; Steventon, G.B.
Phenylalanine 4-monooxygenase and the S-oxidation of S-carboxymethyl-L-cysteine in HepG2 cells
Drug Metabol. Drug Interact.
21
1-18
2005
Homo sapiens
Manually annotated by BRENDA team
Pey, A.L.; Martinez, A.; Charubala, R.; Maitland, D.J.; Teigen, K.; Calvo, A.; Pfleiderer, W.; Wood, J.M.; Schallreuter, K.U.
Specific interaction of the diastereomers 7(R)- and 7(S)-tetrahydrobiopterin with phenylalanine hydroxylase: implications for understanding primapterinuria and vitiligo
FASEB J.
20
2130-2132
2006
Homo sapiens (P00439)
Manually annotated by BRENDA team
Kozak, L.; Hrabincova, E.; Kintr, J.; Horky, O.; Zapletalova, P.; Blahakova, I.; Mejstrik, P.; Prochazkova, D.
Identification and characterization of large deletions in the phenylalanine hydroxylase (PAH) gene by MLPA: evidence for both homologous and non-homologous mechanisms of rearrangement
Mol. Genet. Metab.
89
300-309
2006
Homo sapiens
Manually annotated by BRENDA team
Lueleyap, H.U.; Alptekin, D.; Pazarba?i, A.; Kasap, M.; Kasap, H.; Demirhindi, H.; Mungan, N.; Ozer, G.; Froster, U.G.
The importance of arginine mutation for the evolutionary structure and function of phenylalanine hydroxylase gene
Mutat. Res.
601
39-45
2006
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Teigen, K.; Jensen, V.R.; Martinez, A.
The reaction mechanism of phenylalanine hydroxylase. - A question of coordination
Pteridines
16
27-34
2005
Chromobacterium violaceum, Homo sapiens, Rattus norvegicus
-
Manually annotated by BRENDA team
Siltberg-Liberles, J.; Martinez, A.
Searching distant homologs of the regulatory ACT domain in phenylalanine hydroxylase
Amino Acids
36
235-249
2008
Homo sapiens
Manually annotated by BRENDA team
Daniele, A.; Cardillo, G.; Pennino, C.; Carbone, M.T.; Scognamiglio, D.; Correra, A.; Pignero, A.; Castaldo, G.; Salvatore, F.
Molecular epidemiology of phenylalanine hydroxylase deficiency in Southern Italy: a 96% detection rate with ten novel mutations
Ann. Hum. Genet.
71
185-193
2007
Homo sapiens
Manually annotated by BRENDA team
Bercovich, D.; Elimelech, A.; Yardeni, T.; Korem, S.; Zlotogora, J.; Gal, N.; Goldstein, N.; Vilensky, B.; Segev, R.; Avraham, S.; Loewenthal, R.; Schwartz, G.; Anikster, Y.
A mutation analysis of the phenylalanine hydroxylase (PAH) gene in the Israeli population
Ann. Hum. Genet.
72
305-309
2008
Homo sapiens
Manually annotated by BRENDA team
Daniele, A.; Cardillo, G.; Pennino, C.; Carbone, M.T.; Scognamiglio, D.; Esposito, L.; Correra, A.; Castaldo, G.; Zagari, A.; Salvatore, F.
Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants
Biochim. Biophys. Acta
1782
378-384
2008
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Wang, L.; Surendran, S.; Michals-Matalon, K.; Bhatia, G.; Tanskley, S.; Koch, R.; Grady, J.; Tyring, S.K.; Stevens, R.C.; Guttler, F.; Matalon, R.
Mutations in the regulatory domain of phenylalanine hydroxylase and response to tetrahydrobiopterin
Genet. Test.
11
174-178
2007
Homo sapiens
Manually annotated by BRENDA team
Zurflueh, M.R.; Zschocke, J.; Lindner, M.; Feillet, F.; Chery, C.; Burlina, A.; Stevens, R.C.; Thoeny, B.; Blau, N.
Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency
Hum. Mutat.
29
167-175
2008
Homo sapiens
Manually annotated by BRENDA team
Eavri, R.; Lorberboum-Galski, H.
A novel approach for enzyme replacement therapy. The use of phenylalanine hydroxylase-based fusion proteins for the treatment of phenylketonuria
J. Biol. Chem.
282
23402-23409
2007
Homo sapiens
Manually annotated by BRENDA team
Yan, S.; Wu, G.
Connecting mutant phenylalanine hydroxylase with phenylketonuria
J. Clin. Monit. Comput.
22
333-342
2008
Homo sapiens (P00439)
Manually annotated by BRENDA team
Patel, N.G.; Iliadou, C.; Boonyapiwat, B.; Barlow, D.J.; Forbes, B.; Mitchell, S.C.; Steventon, G.B.
Enzyme kinetic and molecular modelling studies of sulphur-containing substrates of phenylalanine 4-monooxygenase
J. Enzyme Inhib. Med. Chem.
23
958-63
2007
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Bercovich, D.; Elimelech, A.; Zlotogora, J.; Korem, S.; Yardeni, T.; Gal, N.; Goldstein, N.; Vilensky, B.; Segev, R.; Avraham, S.; Loewenthal, R.; Schwartz, G.; Anikster, Y.
Genotype-phenotype correlations analysis of mutations in the phenylalanine hydroxylase (PAH) gene
J. Hum. Genet.
53
407-418
2008
Homo sapiens
Manually annotated by BRENDA team
Gramer, G.; Burgard, P.; Garbade, S.F.; Lindner, M.
Effects and clinical significance of tetrahydrobiopterin supplementation in phenylalanine hydroxylase-deficient hyperphenylalaninaemia
J. Inherit. Metab. Dis.
30
556-562
2007
Homo sapiens
Manually annotated by BRENDA team
Dobrowolski, S.F.; Ellingson, C.; Coyne, T.; Grey, J.; Martin, R.; Naylor, E.W.; Koch, R.; Levy, H.L.
Mutations in the phenylalanine hydroxylase gene identified in 95 patients with phenylketonuria using novel systems of mutation scanning and specific genotyping based upon thermal melt profiles
Mol. Genet. Metab.
91
218-227
2007
Homo sapiens (Q8TEY0), Homo sapiens
Manually annotated by BRENDA team
Okano, Y.; Takatori, K.; Kudo, S.; Sakaguchi, T.; Asada, M.; Kajiwara, M.; Yamano, T.
Effects of tetrahydrobiopterin and phenylalanine on in vivo human phenylalanine hydroxylase by phenylalanine breath test
Mol. Genet. Metab.
92
308-314
2007
Homo sapiens
Manually annotated by BRENDA team
Nascimento, C.; Leandro, J.; Tavares de Almeida, I.; Leandro, P.
Modulation of the activity of newly synthesized human phenylalanine hydroxylase mutant proteins by low-molecular-weight compounds
Protein J.
27
392-400
2008
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Boonyapiwat, B.; Forbes, B.; Mitchell, S.; Steventon, G.B.
Phenylalanine 4-monooxygenase and the S-oxidation of S-carboxymethyl-L-cysteine by human cytosolic fractions
Drug Metabol. Drug Interact.
23
261-282
2008
Homo sapiens
Manually annotated by BRENDA team
Lee, Y.W.; Lee, D.H.; Kim, N.D.; Lee, S.T.; Ahn, J.Y.; Choi, T.Y.; Lee, Y.K.; Kim, S.H.; Kim, J.W.; Ki, C.S.
Mutation analysis of PAH gene and characterization of a recurrent deletion mutation in Korean patients with phenylketonuria
Exp. Mol. Med.
40
533-540
2008
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Steventon, G.B.; Mitchell, S.C.
Phenylalanine 4-monooxygenase and the role of endobiotic metabolism enzymes in xenobiotic biotransformation
Expert. Opin. Drug Metab. Toxicol.
5
1213-1221
2009
Rattus norvegicus, Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Brenner, E.; Smagulova, F.; Morozov, I.
Independent origin of rare Y168H mutation of human phenylalanine hydroxylase gene in Russia
Genetika
44
1435-1437
2008
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Patel, N.; Iliadou, C.; Boonyapiwat, B.; Barlow, D.; Forbes, B.; Mitchell, S.; Steventon, G.
Enzyme kinetic and molecular modelling studies of sulphur-containing substrates of phenylalanine 4-monooxygenase
J. Enzyme Inhib. Med. Chem.
23
958-963
2008
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Dobrowolski, S.F.; Borski, K.; Ellingson, C.C.; Koch, R.; Levy, H.L.; Naylor, E.W.
A limited spectrum of phenylalanine hydroxylase mutations is observed in phenylketonuria patients in western Poland and implications for treatment with 6R tetrahydrobiopterin
J. Hum. Genet.
54
335-339
2009
Homo sapiens
Manually annotated by BRENDA team
Dobrowolski, S.F.; Pey, A.L.; Koch, R.; Levy, H.; Ellingson, C.C.; Naylor, E.W.; Martinez, A.
Biochemical characterization of mutant phenylalanine hydroxylase enzymes and correlation with clinical presentation in hyperphenylalaninaemic patients
J. Inherit. Metab. Dis.
32
10-21
2009
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Boonyapiwat, B.; Panaretou, B.; Forbes, B.; Mitchell, S.C.; Steventon, G.B.
Human phenylalanine monooxygenase and thioether metabolism
J. Pharm. Pharmacol.
61
63-67
2009
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Bik-Multanowski, M.; Pietrzyk, J.; Didycz, B.; Szymczakiewicz-Multanowska, A.
Development of a model for assessment of phenylalanine hydroxylase activity in newborns with phenylketonuria receiving tetrahydrobiopterin: A potential for practical implementation
Mol. Genet. Metab.
94
389-390
2008
Homo sapiens (P00439)
Manually annotated by BRENDA team
Steventon, G.B.; Mitchell, S.C.; Perez, B.; Desviat, L.R.; Ugarte, M.
The activity of wild type and mutant phenylalanine hydroxylase with respect to the C-oxidation of phenylalanine and the S-oxidation of S-carboxymethyl-L-cysteine
Mol. Genet. Metab.
96
27-31
2009
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Stojiljkovic, M.; Perez, B.; Desviat, L.R.; Aguado, C.; Ugarte, M.; Pavlovic, S.
The missense p.S231F phenylalanine hydroxylase gene mutation causes complete loss of enzymatic activity in vitro
Protein J.
28
294-299
2009
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Leandro, J.; Leandro, P.; Flatmark, T.
Heterotetrameric forms of human phenylalanine hydroxylase: co-expression of wild-type and mutant forms in a bicistronic system
Biochim. Biophys. Acta
1812
602-612
2011
Homo sapiens
Manually annotated by BRENDA team
Gersting, S.W.; Staudigl, M.; Truger, M.S.; Messing, D.D.; Danecka, M.K.; Sommerhoff, C.P.; Kemter, K.F.; Muntau, A.C.
Activation of phenylalanine hydroxylase induces positive cooperativity toward the natural cofactor
J. Biol. Chem.
285
30686-30697
2010
Homo sapiens
Manually annotated by BRENDA team
Boonyapiwat, B.; Mitchell, S.; Steventon, G.
Recombinant heteromeric phenylalanine monooxygenase and the oxygenation of carbon and sulfur substrates
J. Pharm. Pharmacol.
63
558-564
2011
Homo sapiens
Manually annotated by BRENDA team
Antypa, A.; Rebello, C.; Biernacka, A.; Krajewski, K.; Cassam, J.; Mitchell, S.C.; Steventon, G.B.
Post-translational activation of human phenylalanine 4-monooxygenase from an endobiotic to a xenobiotic enzyme by reactive oxygen and reactive nitrogen species
Xenobiotica
40
319-330
2010
Homo sapiens
Manually annotated by BRENDA team
Jaffe, E.K.; Stith, L.; Lawrence, S.H.; Andrake, M.; Dunbrack, R.L.
A new model for allosteric regulation of phenylalanine hydroxylase: implications for disease and therapeutics
Arch. Biochem. Biophys.
530
73-82
2013
Homo sapiens, Rattus norvegicus (P04176)
Manually annotated by BRENDA team
Daubner, S.C.; Avila, A.; Bailey, J.O.; Barrera, D.; Bermudez, J.Y.; Giles, D.H.; Khan, C.A.; Shaheen, N.; Thompson, J.W.; Vasquez, J.; Oxley, S.P.; Fitzpatrick, P.F.
Mutagenesis of a specificity-determining residue in tyrosine hydroxylase establishes that the enzyme is a robust phenylalanine hydroxylase but a fragile tyrosine hydroxylase
Biochemistry
52
1446-1455
2013
Homo sapiens (P00439)
Manually annotated by BRENDA team
Flydal, M.I.; Martinez, A.
Phenylalanine hydroxylase: function, structure, and regulation
IUBMB Life
65
341-349
2013
Caenorhabditis elegans, Legionella pneumophila, Homo sapiens (P00439), Homo sapiens, Rattus norvegicus (P04176), Chromobacterium violaceum (P30967), Colwellia psychrerythraea (Q47XN7), Legionella pneumophila 130b
Manually annotated by BRENDA team
Carluccio, C.; Fraternali, F.; Salvatore, F.; Fornili, A.; Zagari, A.
Structural features of the regulatory ACT domain of phenylalanine hydroxylase
PLoS ONE
8
e79482
2013
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Shi, Z.; Sellers, J.; Moult, J.
Protein stability and in vivo concentration of missense mutations in phenylalanine hydroxylase
Proteins
80
61-70
2012
Homo sapiens
Manually annotated by BRENDA team
Hayakawa, D.; Yamaotsu, N.; Nakagome, I.; Ozawa, S.I.; Yoshida, T.; Hirono, S.
In silico analyses of the effects of a point mutation and a pharmacological chaperone on the thermal fluctuation of phenylalanine hydroxylase
Biophys. Chem.
228
47-54
2017
Homo sapiens (P00439)
Manually annotated by BRENDA team
Ramirez, A.M.; Rodriguez-Lopez, A.; Ardila, A.; Beltran, L.; Patarroyo, C.A.; Melendez, A.D.P.; Sanchez, O.F.; Almeciga-Diaz, C.J.
Production of human recombinant phenylalanine hydroxylase in Lactobacillus plantarum for gastrointestinal delivery
Eur. J. Pharm. Sci.
109
48-55
2017
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Leandro, J.; Stokka, A.J.; Teigen, K.; Andersen, O.A.; Flatmark, T.
Substituting Tyr138 in the active site loop of human phenylalanine hydroxylase affects catalysis and substrate activation
FEBS Open Bio
7
1026-1036
2017
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Leandro, J.; Saraste, J.; Leandro, P.; Flatmark, T.
PKU mutation p.G46S prevents the stereospecific binding of L-phenylalanine to the dimer of human phenylalanine hydroxylase regulatory domain
FEBS open bio
7
195-203
2017
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Pecimonova, M.; Polak, E.; Csicsay, F.; Reblova, K.; Stojiljkovic, M.; Levarski, Z.; Skultety, L.; Kadasi, L.; Soltysova, A.
Functional and structural characterisation of 5 missense mutations of the phenylalanine hydroxylase
Gen. Physiol. Biophys.
36
361-371
2017
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Yu, W.; He, J.; Yang, X.; Zou, H.; Gui, J.; Wang, R.; Yang, L.; Wang, Z.; Lei, Q.
Characterization of phenylalanine hydroxylase gene mutations in phenylketonuria in Xinjiang of China
Int. J. Clin. Exp. Med.
7
4406-4412
2014
Homo sapiens
Manually annotated by BRENDA team
Meisburger, S.P.; Taylor, A.B.; Khan, C.A.; Zhang, S.; Fitzpatrick, P.F.; Ando, N.
Domain movements upon activation of phenylalanine hydroxylase characterized by crystallography and chromatography-coupled small-angle X-ray scattering
J. Am. Chem. Soc.
138
6506-6516
2016
Homo sapiens (P00439), Rattus norvegicus (P04176)
Manually annotated by BRENDA team
Chadha, N.; Tiwari, A.K.; Kumar, V.; Milton, M.D.; Mishra, A.K.
In silico thermodynamics stability change analysis involved in BH4 responsive mutations in phenylalanine hydroxylase QM/MM and MD simulations analysis
J. Biomol. Struct. Dyn.
33
573-583
2015
Homo sapiens (P00439)
Manually annotated by BRENDA team
Carluccio, C.; Fraternali, F.; Salvatore, F.; Fornili, A.; Zagari, A.
Towards the identification of the allosteric Phe-binding site in phenylalanine hydroxylase
J. Biomol. Struct. Dyn.
34
497-507
2016
Cupriavidus necator, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas fluorescens, Xanthomonas campestris, Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Reblova, K.; Kulhanek, P.; Fajkusova, L.
Computational study of missense mutations in phenylalanine hydroxylase
J. Mol. Model.
21
70
2015
Homo sapiens (P00439)
Manually annotated by BRENDA team
Baruteau, J.; Nyabi, O.; Najimi, M.; Fauvart, M.; Sokal, E.
Adult human liver mesenchymal progenitor cells express phenylalanine hydroxylase
J. Pediatr. Endocrinol. Metab.
27
863-868
2014
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Shen, N.; Heintz, C.; Thiel, C.; Okun, J.G.; Hoffmann, G.F.; Blau, N.
Co-expression of phenylalanine hydroxylase variants and effects of interallelic complementation on in vitro enzyme activity and genotype-phenotype correlation
Mol. Genet. Metab.
117
328-335
2016
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team
Fuchs, J.; Fuchs, D.; Liedl, K.
Dynamic regulation of phenylalanine hydroxylase
Pteridines
25
33-39
2014
Homo sapiens
-
Manually annotated by BRENDA team
Patel, D.; Kopec, J.; Fitzpatrick, F.; McCorvie, T.J.; Yue, W.W.
Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain
Sci. Rep.
6
23748
2016
Homo sapiens (P00439), Homo sapiens
Manually annotated by BRENDA team