Information on EC 1.14.16.1 - phenylalanine 4-monooxygenase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

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EC NUMBER
COMMENTARY hide
1.14.16.1
-
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RECOMMENDED NAME
GeneOntology No.
phenylalanine 4-monooxygenase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
oxygenation
-
S-oxygenation
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
L-phenylalanine degradation I (aerobic)
-
-
L-phenylalanine degradation V
-
-
L-tyrosine biosynthesis IV
-
-
Metabolic pathways
-
-
Phenylalanine metabolism
-
-
Phenylalanine, tyrosine and tryptophan biosynthesis
-
-
phenylalanine metabolism
-
-
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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-hydroxytetrahydrobiopterin formed can dehydrate to 6,7-dihydrobiopterin, both spontaneously and by the action of EC 4.2.1.96, 4a-hydroxytetrahydrobiopterin dehydratase. The 6,7-dihydrobiopterin can be enzymically reduced back to tetrahydrobiopterin, by EC 1.5.1.34, 6,7-dihydropteridine reductase, or slowly rearranges into the more stable compound 7,8-dihydrobiopterin.
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CAS REGISTRY NUMBER
COMMENTARY hide
9029-73-6
-
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
Swissprot
Manually annotated by BRENDA team
field mouse
-
-
Manually annotated by BRENDA team
-
Swissprot
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Schreber, bank vole
-
-
Manually annotated by BRENDA team
strain NBRC 12614T
SwissProt
Manually annotated by BRENDA team
a psychrophilic bacterium
-
-
Manually annotated by BRENDA team
-
Uniprot
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Wistar
-
-
Manually annotated by BRENDA team
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
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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
-
-
?
2-fluorophenylalanine + tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
3-(2-thienyl)-L-alanine + 6-methyltetrahydropterin + O2
? + 6-methyldihydropterin + H2O
show the reaction diagram
-
-
-
-
?
3-(2-thienyl)-L-alanine + tetrahydrobiopterin + O2
? + dihydrobiopterin + H2O
show the reaction diagram
-
-
-
-
?
3-fluorophenylalanine + tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
3-phenylserine + tetrahydrobiopterin + O2
?
show the reaction diagram
4-chlorophenylalanine + tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
4-fluorophenylalanine + tetrahydrobiopterin + O2
?
show the reaction diagram
4-methyl-L-phenylalanine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
4-methylphenylalanine + 6,7-dimethyl-tetrahydropterin + O2
4-(hydroxymethyl)phenylalanine + 3-methyltyrosine + H2O + 6,7-dimethyl-dihydropterin
show the reaction diagram
beta-2-thienylalanine + tetrahydrobiopterin + O2
?
show the reaction diagram
-
-
-
-
?
L-cyclohexylalanine + 6,7-dimethyl-tetrahydropterin + O2
4-hydroxy-L-cyclohexylalanine + H2O + 6,7-dimethyl-dihydropterin
show the reaction diagram
L-methionine + 5,6,7,8-tetrahydrobiopterin + O2
?
show the reaction diagram
L-methionine + tetrahydrobiopterin + O2
?
show the reaction diagram
-
lysolecithin activated enzyme
-
-
?
L-norleucine + tetrahydrobiopterin + O2
?
show the reaction diagram
-
lysolecithin activated enzyme
-
-
?
L-norleucine + tetrahydrobiopterin + O2
? + dihydrobiopterin + H2O
show the reaction diagram
-
5% of the activity with 3-(2-thienyl)-L-alanine
-
-
?
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 + (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-phenylalanine + (6R)-tetrahydrobiopterin + O2
L-tyrosine + (6R)-dihydrobiopterin + H2O
show the reaction diagram
-
in mammals rate-limiting step in complete catabolism of phenylalanine to CO2 and water
-
?
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-hydroxy-tetrahydrobiopterin
show the reaction diagram
L-phenylalanine + 5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
L-phenylalanine + 6,7-dimethyl-5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 7,8-dimethyl-6,7-dihydrobiopterin + H2O
show the reaction diagram
-
-
-
-
-
L-phenylalanine + 6,7-dimethyl-tetrahydrobiopterin + O2
L-tyrosine + 6,7-dimethyl-4a-hydroxy-tetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-phenylalanine + 6,7-dimethyltetrahydropterin + O2
4-(hydroxymethyl)phenylalanine + 3-methyltyrosine + H2O + 6,7-dimethyl-dihydropterin
show the reaction diagram
-
-
-
-
?
L-phenylalanine + 6-methyl-tetrahydrobiopterin + O2
L-tyrosine + 6-methyl-4-hydroxy-tetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-phenylalanine + 6-methyl-tetrahydrobiopterin + O2
L-tyrosine + 6-methyl-4a-hydroxy-tetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-phenylalanine + 6-methyltetrahydrobiopterin + O2
L-tyrosine + 6-methyl-4a-hydroxytetrahydrobiopterin
show the reaction diagram
-
-
-
-
?
L-phenylalanine + 6-methyltetrahydropterin + O2
2-amino-4a-hydroxy-7-methyl-5,6,7,8-tetrahydropteridin-4(4aH)-one + H2O + ?
show the reaction diagram
-
-
-
-
?
L-phenylalanine + 6-methyltetrahydropterin + O2
?
show the reaction diagram
-
-
-
-
?
L-phenylalanine + 6-methyltetrahydropterin + O2
L-phenylalanine + 6-methyldihydropterin + H2O2
show the reaction diagram
-
copper-depleted enzyme, in the absence of Fe2+, 6-methyltetrahydropterin oxidation can be uncoupled from substrate hydroxylation by the exclusion of iron
-
?
L-phenylalanine + 6-methyltetrahydropterin + O2
L-tyrosine + 4a-hydroxy-6-methyltetrahydropterin
show the reaction diagram
-
low activity with 6-methyltetrahydropterin
-
-
?
L-phenylalanine + 6-methyltetrahydropterin + O2
L-tyrosine + 6-methyldihydropterin + H2O
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 + 5,6,7,8-tetrahydrobiopterin + O2
5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin
show the reaction diagram
L-tryptophan + tetrahydrobiopterin + O2
?
show the reaction diagram
m-tyrosine + tetrahydrobiopterin + O2
?
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
p-methylphenylalanine + tetrahydrobiopterin + O2
?
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
S-carboxy-methyl-L-cysteine + 5,6,7,8-tetrahydrobiopterin + O2
S-carboxymethyl-L-cysteine S-oxide + dihydrobiopterin + H2O
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 + 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
S-methyl-L-cysteine + O2
?
show the reaction diagram
S-methyl-L-cysteine + tetrahydrobiopterin + O2
?
show the reaction diagram
-
lysolecithin activated enzyme
-
-
?
S-methyl-L-cysteine + tetrahydrobiopterin + O2
S-methyl-L-cysteine S-oxide + dihydrobiopterin + H2O
show the reaction diagram
additional information
?
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
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 + (6R)-tetrahydrobiopterin + O2
L-tyrosine + (6R)-dihydrobiopterin + H2O
show the reaction diagram
-
in mammals rate-limiting step in complete catabolism of phenylalanine to CO2 and water
-
?
L-phenylalanine + 5,6,7,8-tetrahydrobiopterin + O2
L-tyrosine + 4a-hydroxy-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
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
?
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(6R)-5,6,7,8-tetrahydro-L-monapterin
-
7% of the activity with tetrahydrobiopterin
(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
5,6,7,8-tetrahydrobiopterin
-
-
6,7-dimethyl-5,6,7,8-tetrahydrobiopterin
-
-
6,7-dimethyltetrahydropterin
-
17% of the activity with tetrahydrobiopterin
6-methyl-tetrahydrobiopterin
6-methyltetrahydrobiopterin
-
-
dihydrobiopterin
-
-
L-threo-neopterin
-
-
tetrahydrobiopterin
tetrahydrofolate
additional information
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
substoichiometric amounts after removal of copper with dithiothreitol
Cl-
-
bound by residue S391
Co2+
-
can substitute for Fe2+, but is less efficient at higher temperature, determination of binding affinity
copper
additional information
-
enzyme does not contain iron
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(6R)-L-erythro-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
-
(7R)-tetrahydrobiopterin
-
slight inhibition, synthetic pathway, overview, conformational structure by NMR
(7S)-tetrahydrobiopterin
-
strong, competitive inhibition, synthetic pathway, overview, conformational structure by NMR
2,2'-dipyridine
-
-
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
2,3-dihydroxynaphthalene
-
binds to Fe3+ on enzyme that is oxidized during catalysis
2-mercaptoethanol
-
2 mM, 80% inhibition
3,4-dihydroxyphenylpropane
-
0.0016 mM, 50% inhibition
3,4-Dihydroxyphenylpropionic acid
-
0.24 mM, 50% inhibition
3,4-Dihydroxystyrene
-
0.0005-0.005 mM, 50% inhibition, noncompetitive vs. 6,7-dimethyltetrahydropterin and L-phenylalanine
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
4-hydroxyphenylpyruvic acid
-
above 0.4 mM iron, activation below
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
7(S)-tetrahydrobiopterin
-
-
8-hydroxyquinoline
-
-
Acetohydroxamate
-
competitive vs. tetrahydrobiopterin, most probably due to chelation of enzyme's iron
ascorbate
-
2 mM, 78% inhibition
Bathocuproine
-
-
bathophenanthroline
-
competitive vs. 6-methyl-5,6,7,8-tetrahydropterin and tetrahydrobiopterin, most probably due to chelation of enzyme's iron
bathophenanthroline disulfonate
-
0.025 mM, 50% inhibition
benzohydroxamate
-
competitive vs. tetrahydrobiopterin, most probably due to chelation of enzyme's iron
catechol
Co2+
-
replaced Fe2+ at the active site
Copper-chelating agents
-
-
-
D,L-DOPA
-
0.1 mM, approx. 60% inhibition
D,L-m-tyrosine
-
0.4 mM, approx. 80% inhibition
deaza-6-methyltetrahydropterin
-
competitive vs. 6-methyltetrahydropterin
deferoxamine
-
5 mM, 1% residual activity
diethyldithiocarbamate
dithiothreitol
DL-alpha-tocopherol
-
strong inhibition
dopamine
epinephrine
-
-
glycerol
-
-
H2O2
-
inactivates the reduced form of the enzyme
halogenated phenylalanine
-
moderate
-
Iron-chelating agents
-
-
-
L-3,4-dihydroxyphenylalanine
-
-
L-cysteine
-
2 mM, 42% inhibition
L-Dopa
-
0.3 mM, approx. 40% inhibition
L-methionine
L-phenylalanine
L-tryptophan
-
-
norepinephrine
-
-
o-phenanthroline
phenylalanine
-
-
S-carboxy-methyl-L-cysteine
S-carboxymethyl-L-cysteine
S-methyl-ergothionine
S-methyl-L-cysteine
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
Tween 80
-
-
tyrosine
additional information
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-hydroxyphenylacetic acid
-
0.4 mM, approx. 30% activation
alpha-chymotrypsin
-
limited proteolysis of purified liver enzyme, 20-30fold increase in activity, cofactor tetrahydrobiopterin
-
cAMP-dependent protein kinase
-
dithiothreitol
glycerol
-
does no affect the wild-type enzyme activity at 1-5%, but increases the activity of the mutant enzymes about 1-3fold, overview
H2O2
-
2 mM, up to 4fold increase in activity, mixed activation mechanism, oxidation of Trp120 to 5-hydroxy-Trp120
L-phenylalanine
liver lysosomal proteases
-
limited proteolysis of liver enzyme
-
lysolecithin
N-ethylmaleimide
-
activation by alkylation of sulfhydryl groups
phenylalanine
Phospholipids
tetrahydrobiopterin
-
excessive dosages of BH4 inhibit PAH under normal phenylalanine conditions in vivo and activate PAH under conditions of high phenylalanine, overview
Trypsin
-
limited proteolysis of purified liver enzyme
-
additional information
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.003 - 0.025
(6R)-5,6,7,8-tetrahydrobiopterin
0.008 - 0.094
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
0.2
(7R)-5,6,7,8-tetrahydrobiopterin
-
recombinant enzyme
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
0.054
2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine
-
-
1
4-Fluorophenylalanine
-
approx. value
0.001 - 0.155
5,6,7,8-tetrahydrobiopterin
0.044
6,7-dimethyl-5,6,7,8-tetrahydrobiopterin
-
-
0.0344 - 0.0444
6,7-dimethyl-5,6,7,8-tetrahydropterin
0.065 - 0.105
6,7-dimethyltetrahydrobiopterin
0.033 - 0.06
6,7-dimethyltetrahydropterin
0.037 - 0.0455
6-Methyl-5,6,7,8-tetrahydropterin
0.063 - 0.083
6-methyl-tetrahydrobiopterin
0.43 - 6.9
6-methyltetrahydrobiopterin
0.01 - 0.1
6-methyltetrahydropterin
0.22
7(R,S)-tetrahydrobiopterin
-
pH 7.0, 25°C, recombinant enzyme
0.008 - 0.028
Abz-VAA
-
0.0024
L-cyclohexylalanine
-
-
3.1 - 7.75
L-methionine
0.1 - 6.9
L-Phe
0.022 - 7.14
L-phenylalanine
1 - 8.5
L-tryptophan
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
55.97 - 63.8
N-acetyl-S-carboxymethyl-L-cysteine
58.92 - 68.25
N-acetyl-S-methyl-L-cysteine
0.043 - 1.3
phenylalanine
4.6 - 14.73
S-carboxy-methyl-L-cysteine
0.0728 - 25.24
S-carboxymethyl-L-cysteine
0.3 - 0.45
S-methyl-ergothionine
18.32 - 51.6
S-methyl-L-cysteine
0.002 - 0.5
tetrahydrobiopterin
0.47 - 1.7
thienylalanine
0.024 - 0.096
tryptophan
additional information
L-phenylalanine
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2 - 0.6
5,6,7,8-tetrahydrobiopterin
3 - 6
6,7-dimethyl-5,6,7,8-tetrahydrobiopterin
Chromobacterium violaceum
-
-
0.9 - 1.4
6,7-dimethyltetrahydropterin
0.031 - 7.85
6-methyl-tetrahydrobiopterin
1.6
6-methyltetrahydropterin
Chromobacterium violaceum
-
wild type enzyme, at 25°C with 50 mM HEPES (pH 7.2), 5 mM dithiothreitol
0.04 - 21.5
L-phenylalanine
0.4 - 2.08
L-tryptophan
0.0183 - 16
phenylalanine
additional information
additional information
Homo sapiens
-
wild-type PAH kinetic analyses using a new assay reveal cooperativity of activated PAH toward (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
-
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.6 - 48
L-phenylalanine
104
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0015
(7R)-5,6,7,8-tetrahydrobiopterin
-
-
0.00027 - 0.0032
3,4-Dihydroxystyrene
1.1
4-Chlorophenylalanine
-
-
0.0023 - 0.0049
7(S)-tetrahydrobiopterin
-
pH 7.0, 25°C, recombinant enzyme, versus (6R)-tetrahydrobiopterin
1.7
Acetohydroxamate
-
-
0.0000015 - 0.0000018
bathophenanthroline
0.07
benzohydroxymate
-
-
-
0.01
catechol
-
-
0.026
deaza-6-methyltetrahydropterin
-
-
3.5 - 8.11
L-methionine
0.3
L-tryptophan
-
competitive vs. iron
0.11
phenylalanine
-
competitive vs. iron
5.01 - 13.14
S-carboxy-methyl-L-cysteine
17.23
S-carboxymethyl-L-cysteine
-
in pooled hepatic cytosolic enzyme fraction, at 37°C
0.41 - 0.5
S-methyl-ergothionine
17.32 - 41.53
S-methyl-L-cysteine
0.3
tyrosine
-
competitive vs. iron
additional information
additional information
-
inhibition kinetics
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00009
-
activity in liver of males living in an area with high emissions of SO2 and nitrogen oxides, cofactor tetrahydrobiopterin
0.00033
-
activity in liver of males, cofactor tetrahydrobiopterin
0.0009
-
mutant enzyme V388M, using S-carboxymethyl-L-cysteine as substrate
0.00097
-
activity in liver of males, cofactor tetrahydrobiopterin
0.0014
-
mutant enzyme I65T, using S-carboxymethyl-L-cysteine as substrate; mutant enzyme R68S, using S-carboxymethyl-L-cysteine as substrate
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
0.006
-
activity in liver of males, cofactor 6,7-dimethyltetrahydropterin
0.055
-
I65T mutant enzyme, cofactor 6-methyltetrahydropterin
0.073
-
wild type enzyme, using S-carboxymethyl-L-cysteine as substrate
0.09
-
cofactor 6,7-dimethyltetrahydropterin
0.099
-
R270K mutant enzyme, expression in the absence of glycerol in the growth medium, cofactor 6-methyltetrahydropterin
0.105
-
activity in liver of males living in an area with high emissions of SO2 and nitrogen oxides, cofactor 6,7-dimethyltetrahydropterin
0.106
-
-
0.17
-
cofactor 6-methyltetrahydropterin
0.225
-
liver enzyme
0.247
-
activity in liver of males, cofactor 6,7-dimethyltetrahydropterin
0.307
mutant enzyme W180F, at 30°C, using L-phenylalanine as substrate
0.342
mutant enzyme W180F, at 30°C, using 5,6,7,8-tetrahydrobiopterin as substrate
0.347
wild type enzyme, at 30°C, using 5,6,7,8-tetrahydrobiopterin as substrate
0.408
-
V388M mutant enzyme, cofactor tetrahydrobiopterin
0.4169
-
non-L-phenylalanine-activated wild type enzyme, at 25°C
0.424
-
maltose-binding-protein phenylalanine hydroxylase fusion protein, dimeric form
0.44
-
liver enzyme
0.505
-
mutant enzyme V388M, using L-phenylalanine as substrate
0.536
-
R261Q mutant enzyme, cofactor tetrahydrobiopterin
0.69
wild type enzyme, at 30°C, using L-tryptophan as substrate
0.7418
-
L-phenylalanine-activated wild type enzyme, at 25°C
0.745
-
V388M mutant enzyme, cofactor 6-methyltetrahydropterin
0.75
-
mutant enzyme R408W, using L-phenylalanine as substrate, in 100 mM Na-HEPES buffer, pH 7.0, at 25°C
0.77
-
mutant R68V, preincubation with L-phenylalanine
0.78
-
R261Q mutant enzyme, cofactor 6-methyltetrahydropterin
0.893
mutant enzyme W180F, at 30°C, using L-tryptophan as substrate
1
mutant enzyme L101Y, at 30°C, using 5,6,7,8-tetrahydrobiopterin as substrate; mutant enzyme L101Y/W180F, at 30°C, using L-phenylalanine as substrate
1.05
mutant enzyme L101Y/W180F, at 30°C, using 5,6,7,8-tetrahydrobiopterin as substrate
1.08
-
mutant C237R
1.1
-
wild-type, preincubation with L-phenylalanine
1.13
-
mutant C237R, preincubation with L-phenylalanine
1.2
-
mutant enzyme Y414C, using L-phenylalanine as substrate
1.283
-
maltose-binding-protein phenylalanine hydroxylase fusion protein, tetrameric form
1.32
-
mutant enzyme R155H, using L-phenylalanine as substrate, in 100 mM Na-HEPES buffer, pH 7.0, at 25°C
1.46
-
; enzyme form II
1.49
-
mutant enzyme R261Q, using L-phenylalanine as substrate
1.6
-
fetal liver enzyme
1.64
-
mutant enzyme D143G, using L-phenylalanine as substrate, in 100 mM Na-HEPES buffer, pH 7.0, at 25°C
1.7
-
pH 7.0, 25°C, wild-type, dimer
1.725
-
mutant enzyme R68S, using L-phenylalanine as substrate
1.742
-
recombinant wild-type enzyme, cofactor tetrahydrobiopterin
1.76
-
adult liver enzyme
1.77
mutant enzyme L101Y, at 30°C, using L-tryptophan as substrate
1.773
-
V388M mutant enzyme, expression in the absence of glycerol in the growth medium, cofactor 6-methyltetrahydropterin
1.8
-
enzyme form I
1.9
-
wild type enzyme, using L-phenylalanine as substrate
1.98
-
substrate L-phenylalanine, mutant N223D
2.1
-
micromol L-Tyr/min/mg, wild-type, pH 7.0, 25°C, without L-Phe preincubated enzyme
2.14
-
mutant R68V
2.2
-
mutant R68A, preincubation with L-phenylalanine
2.25
-
mutant enzyme I65T, using L-phenylalanine as substrate
2.34
-
substrate tetrahydrobiopterin, mutant N223D
2.49
-
recombinant wild-type enzyme, cofactor 6-methyltetrahydropterin
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
2.94
-
mutant R68A
2.97
-
mutant C237A
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
3.25
-
wild-type
3.32
-
mutant enzyme P416Q, using L-phenylalanine as substrate, in 100 mM Na-HEPES buffer, pH 7.0, at 25°C
3.37
wild type enzyme, at 30°C, using L-phenylalanine as substrate
3.48
-
substrate L-phenylalanine, wild-type
3.62
mutant enzyme L101Y/W180F, at 30°C, using L-tryptophan as substrate
3.67
-
substrate L-phenylalanine, mutant N426D
3.74
-
substrate L-phenylalanine, mutant N32D
3.81
-
mutant C237D
4.19
-
mutant C237D, preincubation with L-phenylalanine
4.37
-
substrate L-phenylalanine, mutant G33A
4.39
-
substrate tetrahydrobiopterin, mutant N426D
4.73
-
substrate tetrahydrobiopterin, mutant G33A; substrate tetrahydrobiopterin, mutant N32D
4.95
-
pH 7.0, 25°C, wild-type, tetramer
5
-
phosphorylated recombinant wild-type enzyme, S16N and S16D mutant enzyme
5.1
-
S16A and S16K mutant enzymes
5.16
-
substrate L-phenylalanine, mutant G33V
5.2
-
S16E and S16Q mutant enzyme
5.32
-
substrate tetrahydrobiopterin, wild-type
6.19
-
substrate L-phenylalanine, mutant K113P
6.41
-
substrate tetrahydrobiopterin, mutant G33V
6.48
-
pH 7.0, 25°C, N-terminal deletion mutant
6.5
-
micromol L-Tyr/min/mg, mutant Q215K/N216Y, pH 7.0, 25°C, with L-Phe preincubated enzyme
6.8
-
recombinant enzyme
8.32
-
pH 7.0, 25°C, N-terminal plus C-terminal deletion mutant
8.56
-
substrate tetrahydrobiopterin, mutant K113P
10.16
mutant enzyme L101Y, at 30°C, using L-phenylalanine as substrate
10.2
-
in 100 mM Na-HEPES, pH 7.0 at 37°C
12.5 - 13
-
-
14
-
truncated enzyme containing C-terminal 334 amino acids
290
-
mutant Y325A, 25°C, pH 7.0
300
-
mutant Y325A, preincubation with L-phenylalanine, 25°C, pH 7.0
1150
-
mutant Y325F, 25°C, pH 7.0
1230
-
wild-type, 25°C, pH 7.0
1310
-
mutant Y325L, 25°C, pH 7.0
1500
-
mutant Y325L, 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
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8
-
assay at
7.3
-
assay at
7.5
-
assay at
7.8
-
assay at
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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
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
27
-
assay at
37
-
assay at
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15 - 42
-
native and recombinant enzyme
additional information
-
between 7°C and 40°C, maximum activity increases exponentially with temperature, below 20°C, KM-value increases and doubles in value at 7°C
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
melanocyte
Manually annotated by BRENDA team
enzyme expression
Manually annotated by BRENDA team
additional information
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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PDB
SCOP
CATH
ORGANISM
UNIPROT
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Chromobacterium violaceum (strain ATCC 12472 / DSM 30191 / JCM 1249 / NBRC 12614 / NCIMB 9131 / NCTC 9757)
Colwellia psychrerythraea (strain 34H / ATCC BAA-681)
Colwellia psychrerythraea (strain 34H / ATCC BAA-681)
Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
13000
-
2 * 13000 (regulatory domain 1-118), gel filtration. In the presence of phenylalanine, the protein elutes earlier from the column, consistent with a conformational change in the presence of the amino acid
25000 - 27000
-
sucrose density gradient centrifugation, gel filtration
26000
-
gel filtration, regulatory domain (amino acids 1-118)
28000
-
1 * 28000, SDS-PAGE
29000
-
recombinant enzyme, gel filtration
30300
-
gel filtration
31000 - 32400
32000 - 34000
-
holo- and apo-enzyme forms display a similar hydrodynamic volume of 32000-34000 Da, apparent molecular mass based on gel filtration
32500
-
2 * 32500, calculated from amino acid sequence
33000
-
1 * 33000, SDS-PAGE
33613
-
1 * 33613, deduced from nucleotide sequence
46200
-
x * 46200, equilibrium sedimentation
49000
-
x * 49000, adult liver enzyme, SDS-PAGE; x * 52000 + x * 49000, fetal liver enzyme, SDS-PAGE
50400
deduced from cDNA
51000 - 55000
-
monomeric form, enzyme exists as monomer, dimer and tetramer
53000
-
x * 53000, recombinant enzyme, SDS-PAGE
54000
-
2 * 54000, fetal liver enzyme, SDS-PAGE
64000
-
gel filtration
94000
-
approximately 94000 Da, SDS-PAGE
95600
-
calculated from amino acid sequence
100000 - 110000
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
200000 - 210000
240000
-
sedimentation equilibrium
275000
-
-
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
homotetramer
monomer
oligomer
-
wild-type and mutant enzymes show different oligomeric states, from dimer to hexamer, overview
tetramer
additional information
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
side-chain modification
additional information
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 0.1 M Na-HEPES, pH 7.0, 0.01 M magnesium chloride hexahydrate, 0.005 M nickel(II) chloride hexahydrate, and 15% (w/v) PEG 3350, or sitting drop vapor diffusion method, using 0.1 M Na-HEPES pH 7.0, 0.01 M magnesium chloride hexahydrate, and 15% (w/v) PEG
-
vapor-diffusion hanging drop method at 4°C, reservoir solution contains 1 ml of 1.65-1.9 M ammonium sulfate, 40-100 mM NaCl and 20 mM HEPES pH 7.5, hanging drops are made using equal volumes of enzyme, 20 mg/ml, and reservoir solution, crystals grow in about one week, crystal structures of Fe-free apoenzyme, Fe3+-bound enzyme and Fe3+ plus 7,8-dihydro-L-biopterin-bound enzyme at 1.7 A, 2.0 A and 1.4 A resolution respectively
-
vapour diffusion, 1 mg enzyme dissolved in 0.1 ml 35% ammonium sulfate, 50 mM acetate, pH 6.0, 1 mM dithiothreitol, reservoir contains 60% ammonium sulfate, crystals appear after 3-4 d at 4°C
-
native enzyme by hanging drop method, 0.001 ml of protein solution containing 10 mg/ml protein in 20 mM Na-HEPES, 200 mM NaCl, pH 7.0, are mixed with 0.001 ml of reservoir solution containing 1.6-1.8 M ammonium sulfate, 100 mM NaCl, and 20 mM NaHepes, pH 7.5, equilibration at 4 °C, 3 weeks, cryoprotection with 25% glycerol, X-ray diffraction structure determination and analysis
-
apo DicPAH and DicPAH complexed with dihydrobiopterin (BH2) and FeIII are crystallized by the hanging-drop vapour-diffusion method. Crystals of apo DicPAH and the DicPAH-BH2-FeIII complex diffract to 2.6 and 2.07 A resolution, respectively, and belong to space group P21, with unit-cell parameters a = 70.02, b = 85.43, c = 74.86 A, beta= 110.12° and a = 70.97, b = 85.33, c = 74.89 A, beta = 110.23°, respectively
-
crystal structure of ternary complex of catalytic domain, Fe2+ form, with tetrahydrobiopterin and 3-(2-thienyl)-L-alanine
-
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
-
in complex with 6(R)-L-erythro-5,6,7,8-tetrahydrobiopterin and substrate analogues 3-(2-thienyl)-L-alanine or L-norleucine
-
native and selenomethyl-labelled enzyme
-
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 60
-
holo-phenylalanine hydroxylase displays a large increase in thermal stability (approximately 15°C upshift in the Tm value) compared with the apoenzyme (melting temperature at 64°C), holo-caPAH shows higher kinetic stability at optimal growth temperature (denaturing approximately 8 times more slowly than the apo form at 55°C)
44 - 76
-
pH 7.4, kinetics of thermal unfolding of apo- and holo-enzymes within the temperature range and with different metal cofactors: native Fe2+, or artificial Zn2+ or Co2+, unfolding profiles, transition-state analysis shows a common mechanism for all enzyme variants, at higher temperatures the unfolding rates of Zn- and Co-PAH are affected significantly by entropy, while the unfolding rates of apo- and Fe-PAH are dominated by enthalpy even at higher temperatures, overview
47
-
50% residual activity after 66 min, presence of Fe(II), after 8 min in presence of EDTA
50
-
V388M mutant enzyme, 50% activity after 10 min
51
-
L348V mutant enzyme, 50% activity after 10 min
52
-
Tm, inactivation
53
-
melting temperature of enzyme, presence of EDTA
59
-
recombinant wild-type enzyme, 50% activity after 10 min
63
-
melting temperature of enzyme, presence of Fe(II)
additional information
-
thermal inactivation profiles of the purified wild-type enzyme, and mutants I65T, R261Q and V388M in absence or presence of 1% glycerol or trimethylamine N-oxide, overview
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
frozen and thawed enzyme is 10-20% less active than before freezing
-
glycerol + EDTA stabilize
-
NaCl or KCl above 200 mM stabilize
-
nonionic detergents e.g. Triton X-100 and Tween 80, 0.03-0.1%, stabilize
-
phenylalanine stabilizes
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 50 mM acetate, pH 6.0, 3 months, 20% loss of activity
-
-70°C, 2 years, no loss of activity
-
-80°C, 1 month, 30% loss of activity
-
-80°C, 1 year, 30% loss of activity
-
-80°C, enzyme concentration 1 mg/ml, several months, no loss of activity
-
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
adult and fetal liver enzyme, monoclonal antibody affinity chromatography
-
affinity chromatography on 6,7-dimethyl-5,6,7,8-tetrahydropterin-Sepharose 4B
-
ammonium sulfate precipitation and DEAE-Sephacel gel filtration
-
ammonium sulfate, Phenyl-Sepharose, DEAE-Sepharose, recombinant enzyme
-
amylose column chromatography
-
distinct forms I and II differing in phosphate content and isoelectric point
-
double truncated mutant enzyme DELTAN1-102/DELTAC428-452
-
fetal, newborn and adult enzyme are probably identical
-
glutathione-Sepharose column chromatography and Superdex S75 gel filtration
-
HiTrap Q column chromatography
-
metal-free enzyme by extraction of copper with dithiothreitol
-
Ni-NTA column chromatography
-
Ni-TED 2000 column chromatography, gel filtration
phenyl Sepharose column chromatography
-
Phenyl-Sepharose, DEAE-Sepharose
-
polyethylene glycol, Phenyl-Sepharose, DEAE-Sepharose
-
protamine, DEAE-Sephadex, acid, DEAE-cellulose, Ultrogel, hydroxylapatite, Blue dextran-phenyl-butylamine-Sepharose
-
pteridine affinity resin, 2 non-interconvertible forms
-
recombinant catalytic core mutant DELTA 117PheH and point mutants thereof from Escherichia coli strain C41(DE3)
-
recombinant enzyme
-
recombinant enzyme from Escherichia coli by anion exchange chromatography and gel filtration
-
recombinant enzyme, partially purified
-
recombinant His-tagged enzyme from Escherichia coli strain BL21 by metal affinity chromatography
-
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 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 maltose-binding protein-PAH fusion protein from Escherichia coli, cleavage of the fusion protein by factor Xa, gel filtration
recombinant maltose-binding-protein phenylalanine hydroxylase fusion protein
-
recombinant wild-type enzyme and deletion mutants
-
recombinant wild-type S16E, S16Q, S16N, S16D, S16A, and S16K mutant enzyme
-
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
-
TALON resin column chromatography and Superdex 200 gel filtration
-
TALON Superflow metal affinity resin column chromatography and Superdex 200 gel filtration
-
truncated enzyme containing the C-terminal 343 amino acids
-
using Ni-NTA chromatography
-
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DicPAH (residue 1-415) is expressed in Escherichia coli
-
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 Escherichia coli
expressed in Escherichia coli as a His-tagged fusion protein
-
expressed in Escherichia coli as a recombinant protein
-
expressed in Escherichia coli as fusion proteins with maltose-binding protein
-
expressed in Escherichia coli BL21 cells
-
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli BL21(DE3)/pLysS cells
-
expressed in Escherichia coli BL21(DE3)pLysS cells
-
expressed in Escherichia coli TB1 cells
-
expression as maltose-binding-protein fusion protein in Escherichia coli circumvents proteolytic degradation by the host cell
-
expression in Escherichia coli
expression of catalytic core mutant DELTA 117PheH and point mutants thereof in Escherichia coli strain C41(DE3)
-
expression of double truncated mutant enzyme DELTAN1-102/DELTAC428-452 in Escherichia coli
-
expression of His-tagged wild-type, I65T, R261Q and V388M mutant enzymes in Escherichia coli
-
expression of truncated enzyme containing the catalytic domain and various mutants in Escherichia coli
-
expression of wild-type and S16E, S16Q, S16N, S16D, S16A, and S16K mutant enzyme 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
-
expression of wild-type, L348V, L349L and V388M mutant enzyme maltose-binding-protein fusions in Escherichia coli and COS cells
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expression of wild-type, R270K and V388M mutant enzymes in the presence of the chemical chaperone glycerol
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gene pah, DNA and amino acid sequence determination and analysis, genotyping of a Southern Italian population, overview
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gene pah, DNA and amino acid sequence determination and analysis, genotyping, overview
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gene pah, DNA and amino acid sequence determination of wild-type and mutant enzymes, genotyping
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gene pah, expression in Escherichia coli
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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
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gene pah, expression of His6-tagged wild-type and mutant enzymes in Escherichia coli
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gene pah, overexpression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
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gene pah-1, expression as maltose-binding protein fusion protein in Escherichia coli
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
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identification and sequence analysis of enzyme mutant genes with exon deletions isolated from 59 czech phenylketonuria patients, multiplex ligation-dependent probe amplification method
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mutant enzymes are expressed in Escherichia coli
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regulatory domain (amino acids 1-118) of rat phenylalanine hydroxylase is expressed in Escherichia coli
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the truncated enzyme PheHDELTA117 is expressed in Escherichia coli BL21(DE3) cells
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truncated enzyme containing the C-terminal 336 amino acids bearing the catalytic domain
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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%
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
L-phenylalanine does not change mRNA level of L-phenylalanine hydroxylase
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Q215K/N216Y
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humanized mutant Q215K/N216Y of cePAH binds 1.4 L-Phe/subunit. This mutant also displays high catalytic activity and certain positive cooperativity for L-Phe. Km for cofactor tetrahydrobiopterin higher compared to wild-type, [S]0.5 (L-Phe) lower compared to wild-type, Vmax (L-Phe) higher compared to wild-type
F258A
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the mutant shows decreased activity and a marked decrease in the affinity for L-phenylalanine
I234D
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mutant shows decreased kcat value for 6,7-dimethyltetrahydropterin compared to the wild type enzyme
L101A
the mutant shows 26% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101C
the mutant shows 47% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101D
the mutant shows 5% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101E
the mutant shows 9% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101F
the mutant shows 133% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101G
the mutant shows 20% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101H
the mutant shows 16% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101I
the mutant shows 51% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101K
the mutant shows 29% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101M
the mutant shows 102% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101N
the mutant shows 15% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101P
the mutant shows 9% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101Q
the mutant shows 30% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101R
the mutant shows 29% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101S
the mutant shows 28% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101T
the mutant shows 26% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101V
the mutant shows 26% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101W
the mutant shows 55% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101Y
the mutant shows 153% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
L101Y/W180F
the double mutant displays higher L-tryptophan hydroxylation activity than the wild type enzyme with a 5.2fold increase in kcat
S230P
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the mutant shows strongly decreased activity and a marked decrease in the affinity for L-phenylalanine
T254A
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the mutant shows decreased activity and a marked decrease in the affinity for L-phenylalanine
W180A
the mutant shows 66% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180C
the mutant shows 119% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180D
the mutant shows 3% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180E
the mutant shows 6% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180F
the mutant shows 204% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180G
the mutant shows 8% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180H
the mutant shows 73% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180I
the mutant shows 113% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180K
the mutant shows 4% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180L
the mutant shows 174% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180M
the mutant shows 166% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180N
the mutant shows 49% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180P
the mutant shows 15% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180Q
the mutant shows 17% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180R
the mutant shows 85% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180S
the mutant shows 46% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180T
the mutant shows 44% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180V
the mutant shows 155% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
W180Y
the mutant shows 115% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
Y155A
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the mutant shows decreased activity and a marked decrease in the affinity for L-phenylalanine
Y179A
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stability and metal binding comparable to wild-type, kcat-value one order of magnitude lower than wild-type, KM-value of L-phenylalanine increases by 10-fold
Y179F
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stability and metal binding comparable to wild-type, kcat-value one order of magnitude lower than wild-type
F258A
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the mutant shows decreased activity and a marked decrease in the affinity for L-phenylalanine
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S230P
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the mutant shows strongly decreased activity and a marked decrease in the affinity for L-phenylalanine
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T254A
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the mutant shows decreased activity and a marked decrease in the affinity for L-phenylalanine
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Y155A
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the mutant shows decreased activity and a marked decrease in the affinity for L-phenylalanine
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L101A
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the mutant shows 26% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
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L101F
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the mutant shows 133% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
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L101I
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the mutant shows 51% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
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L101W
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the mutant shows 55% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
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L101Y
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the mutant shows 153% relative L-tryptophan hydroxylation activity compared to the wild type enzyme
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A202T
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the mutation is associated with phenylketonuria
A259V
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the mutant with wild type activity exhibits less than 50% of wild type protein level and leads to classic phenyletonuria
A300S
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naturally occuring mutation involved in hyperphenylalaninemia and/or in phenylketonuria, overview
A309V
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the mutant shows 70% of wild type activity
A322G
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the mutant shows 75% of wild type activity
A395G
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naturally occuring mutation involved in hyperphenylalaninemia and/or in phenylketonuria, overview
C237A
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increase of basal activity and affinity for substrate L-phenylalanine
C237R
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reduced activity, elimination of positive cooperativity
C237S
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approx. 2fold higher activity than wild-type
D143G
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mutant with a mild misfolding defect associated with phenylketonuria
D415N
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naturally occuring missense mutation causing a mild phenylketonuria phenotype
DELTA1-102
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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
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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
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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)
E178G
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exon 6 A533G mutation naturally occuring in phenylketonuria patients from the Cukurova region in Turkey, sequence determination and analysis
E280K
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inactive; the mutant shows 2% of wild type activity
E76G
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the mutant shows 65% of wild type activity; the mutant shows 85% of wild type activity
F161S
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the mutant with wild type activity exhibits less than 50% of wild type protein level
F382L
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naturally occuring mutation and site-directed mutagenesis, the mutant shows 44% reduced activity compared to the wild-type enzyme, analysis of structural alterations
F39C
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the mutant enzyme shows reduced activity compared to the wild type
F39L/F55fsdelT
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naturally occuring mutation in the regulatory domain, that affects enzyme activity and causes an atypical form of phenylketonuria
F39L/P281L
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naturally occuring mutation in the regulatory domain, that affects enzyme activity and causes the classical form of phenylketonuria
F39L/R408W
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naturally occuring mutation in the regulatory domain, that affects enzyme activity and causes the classical form of phenylketonuria
G103S
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site-directed mutagenesis, the mutation occurs naturally in phenylketonuria patients from Korea, the mutant shows highly reduced activity compared to the wild-type
G218V
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the mutant shows wild type activity
G247R
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the mutation is associated with phenylketonuria
G247V
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the mutant shows 4% of wild type activity
G332E
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the mutation is associated with phenylketonuria
G332V
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site-directed mutagenesis, the mutation occurs naturally in phenylketonuria patients from Korea, inactive mutant
G33A
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increased basal activity, reduced activation by preincubation with substrate
G33V
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increased basal activity, reduced activation by preincubation with substrate
G344D
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the mutation is associated with phenylketonuria
H271Q
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naturally occuring knockout missense mutation leading to a severe phenylketonuria phenotype
I174V
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naturally occuring missense mutation causing a mild phenylketonuria phenotype
I65S
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the mutant enzyme shows reduced activity compared to the wild type
I65T/R408W
I65T/R68S
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naturally occuring mutation in the regulatory domain, that affects enzyme activity and causes a mild form of phenylketonuria
I65V
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the mutant enzyme shows reduced activity compared to the wild type
I95F
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naturally occuring missense mutation causing a mild phenylketonuria phenotype
I97L
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naturally occuring mutation in the regulatory domain, that affects enzyme activity and is involved in the disorder hyperphenylalaninemia
K113P
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increased basal activity, reduced activation by preincubation with substrate, increase in positive cooperativity
K398K
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naturally occuring mutation
K398N
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naturally occuring mutation and site-directed mutagenesis, the mutant shows 45% reduced activity compared to the wild-type enzyme, analysis of structural alterations
K42I
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the mutant shows 12% of wild type activity
L197F
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naturally occuring knockout missense mutation leading to a severe phenylketonuria phenotype
L212P
naturally occuring mutation involved in phenylketonuria
L255S
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the mutant shows 3% of wild type activity
L255V
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the mutant shows 13% of wild type activity
L293M
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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
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the mutant with wild type activity exhibits less than 50% of wild type protein level and leads to classic phenyletonuria
L41F
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the mutant shows 10% of wild type activity
N223D
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low basal activity, little activation by preincubation with substrate, increase in positive cooperativity
N223Y
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naturally occuring mutation and site-directed mutagenesis, the mutant shows 30% reduced activity compared to the wild-type enzyme, analysis of structural alterations
N32D
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low basal activity, close to normal activation by preincubation with substrate
N426D
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low basal activity, close to normal activation by preincubation with substrate
P122Q
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the mutant with wild type activity exhibits less than 50% of wild type protein level
P225T
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naturally occuring knockout missense mutation leading to a severe phenylketonuria phenotype
P244L
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the mutant shows 68% of wild type activity
P366H
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naturally occuring mutation involved in hyperphenylalaninemia and/or in phenylketonuria, overview
P416Q
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the mutant retains significant catalytic activity yet is observed in classic and moderate phenylketonuria patients
P69S
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site-directed mutagenesis, the mutation occurs naturally in phenylketonuria patients from Korea, the mutant shows reduced activity compared to the wild-type
Q419R
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naturally occuring mutation and site-directed mutagenesis, the mutant shows 29% reduced activity compared to the wild-type enzyme, analysis of structural alterations
R111X
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the mutation is associated with phenylketonuria
R155H
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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
R157N
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the mutant with wild type activity exhibits less than 50% of wild type protein level
R158W
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naturally occuring mutation involved in hyperphenylalaninemia and/or in phenylketonuria, overview
R176X
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the mutation is associated with phenylketonuria
R243X
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exon 6 C727T mutation naturally occuring in phenylketonuria patients from the Cukurova region in Turkey, sequence determination and analysis
R252G
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the mutant with wild type activity exhibits less than 50% of wild type protein level and leads to classic phenyletonuria
R252Q
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the mutant with wild type activity exhibits less than 50% of wild type protein level and leads to classic phenyletonuria
R261P
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naturally occuring missense mutation causing a mild phenylketonuria phenotype
R270S
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the mutant shows 3% of wild type activity
R297C
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naturally occuring mutation
R297H
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naturally occuring mutation
R297L
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naturally occuring mutation and site-directed mutagenesis, the mutant shows 58% reduced activity compared to the wild-type enzyme, analysis of structural alterations
R408W/I283F
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the mutant shows 2% residual activity compared to the wild type enzyme
R408W/I306V
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the mutant shows 18% residual activity compared to the wild type enzyme
R408W/P281L
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inactive
R408W/pA403V
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the mutant shows 20% residual activity compared to the wild type enzyme
R408W/R158Q
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the mutant shows 5% residual activity compared to the wild type enzyme
R408W/R297H
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the mutant shows 15% residual activity compared to the wild type enzyme
R408W/R408W
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inactive
R53H
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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
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increase of basal activity and affinity for substrate L-phenylalanine
R68G
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the mutant shows wild type activity
R68S/R408W
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naturally occuring mutation in the regulatory domain, that affects enzyme activity and causes an atypical form of phenylketonuria
R68V
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little decrease in activity
R71C
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naturally occuring mutation in the regulatory domain, that affects enzyme activity and is involved in the disorder hyperphenylalaninemia
R86S
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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
S231F
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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
S348L
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instable enzyme forming aggregates after expression in Escherichia coli in the presence of GroESL
S349L
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inactive
S391I
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site-directed mutagenesis, the mutation occurs naturally in phenylketonuria patients from Korea, inactive mutant
T278I
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the mutation is associated with phenylketonuria
V106A
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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
V379D/H264Q
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the mutant shows significant activity at tyrosine hydroxylation and a 3000fold decrease in preference for phenylalanine over tyrosine as the substrate
W187X
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the mutation is associated with phenylketonuria
Y166X
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the mutation is associated with phenylketonuria
Y168H
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the mutation is associated with phenylketonuria
Y204C
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the mutation is associated with phenylketonuria
Y277D
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inactive
Y325L
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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
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aggregation after purification, not suitable for characterization
Y356X
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the mutation is associated with phenylketonuria
Y386C
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exon 11 A1157G mutation naturally occuring in phenylketonuria patient from the Cukurova region in Turkey, sequence determination and analysis
A322S/V379D
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truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
DELTA1-117
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mutant lacking the first 117 amino acids containing only the catalytic and tetramerization domains: the effects of phenylalanine on the hydrogen/deuterium exchange kinetics are limited to peptides surrounding the binding site for the amino acid substrate
E280A
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site-directed mutagenesis of catalytic core mutant DELTA117PheH, 70% reduced activity but unaltered isotopic effects of isotope substrates
E330H
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site-directed mutagenesis of a metal ligand binding residue, the mutant enzyme shows over 80% reduced activity compared to the wild-type enzyme
E330Q
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site-directed mutagenesis of a metal ligand binding residue, the mutant enzyme shows over 80% reduced activity compared to the wild-type enzyme
F263A
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site-directed mutagenesis of catalytic core mutant DELTA117PheH, 85% reduced activity but unaltered isotopic effects of isotope substrates
H264Q
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mutant of full length enzyme, no tyrosine hydroxylation activity
H264Q/V379D
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double mutant of full length enzyme, shows significant tyrosine hydroxylation activity; truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
H264Q/Y277H/V379D
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triple mutant of full length enzyme, shows significant tyrosine hydroxylation activity; truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
H285E
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site-directed mutagenesis of a metal ligand binding residue, the mutant enzyme shows over 80% reduced activity compared to the wild-type enzyme
H285Q
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site-directed mutagenesis of a metal ligand binding residue, the mutant enzyme shows 80% reduced activity compared to the wild-type enzyme
H290E
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site-directed mutagenesis of a metal ligand binding residue, the mutant enzyme shows over 80% reduced activity compared to the wild-type enzyme
H290Q
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site-directed mutagenesis of a metal ligand binding residue, the mutant enzyme shows over 80% reduced activity compared to the wild-type enzyme
L293M
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truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
S16A
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similar Km for tetrahydrobiopterin and activity as wild-type
S16D
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similar Km for tetrahydrobiopterin and activity as wild-type
S16E
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slightly higher Km for tetrahydrobiopterin than wild-type, approx. 3fold higher Vmax with phenylalanine
S16K
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similar Km for tetrahydrobiopterin and activity as wild-type
S16N
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slightly higher Km for tetrahydrobiopterin than wild-type, approx. 3fold higher Vmax with phenylalanine
S16Q
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slightly higher Km for tetrahydrobiopterin than wild-type, similar Vmax with phenylalanine
S251A
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truncated enzyme containing the catalytic domain, no tyrosine hydroxylation activity
S251A/H264Q
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truncated enzyme containing the catalytic domain, no tyrosine hydroxylation activity
S251A/H264Q/V379D
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truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
S251A/H264Q/Y277H
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truncated enzyme containing the catalytic domain, no tyrosine hydroxylation activity
S251A/H264Q/Y277H/A322S
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truncated enzyme containing the catalytic domain, no tyrosine hydroxylation activity
S251A/H264Q/Y277H/A322S/V379D
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truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
S251A/H264Q/Y277H/A322S/V379D/Y356H
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truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
S251A/H264Q/Y277H/A322S/V379D/Y356H/L293M
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truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
S251A/H264Q/Y277H/V379D
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truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
S251A/V379D
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truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
Y277H
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mutant of full length enzyme, no tyrosine hydroxylation activity
Y277H/V379D
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truncated enzyme containing the catalytic domain, mutant shows tyrosine hydroxylation activity
additional information
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
molecular biology
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Show AA Sequence (1068 entries)
Please use the Sequence Search for a specific query.
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LINKS TO OTHER DATABASES (specific for EC-Number 1.14.16.1)
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KEGG
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NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM
IUBMB Enzyme Nomenclature
PROSITE Database of protein families and domains
SYSTERS
Protein Mutant Database
InterPro (database of protein families, domains and functional sites)