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Literature summary for 1.14.16.2 extracted from

  • Royo, M.; Daubner, S.C.; Fitzpatrick, P.F.
    Effects of mutations in tyrosine hydroxylase associated with progressive dystonia on the activity and stability of the protein (2004), Proteins, 58, 14-21.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli Homo sapiens

Protein Variants

Protein Variants Comment Organism
R306H 1.2fold decrease in Km-value for L-tyrosine compared to wild-type enzyme, Ki-value for L-tyrosine is nearly identical to wild-type value, 1.3fold decrease in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 1.2fold increase of turnover-number compared to wild-type enzyme. 8.2°C increase in Tm-value compared to wild-type enzyme Homo sapiens
R306H/T463M all of the TyrH is insoluble and no enzyme can be purified Homo sapiens
T245P 1.4fold increase in Km-value for L-tyrosine compared to wild-type enzyme, 1.6fold increase in Ki-value for L-tyrosine compared to wild-type enzyme, 1.1fold increase in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 1.6fold increase of turnover-number compared to wild-type enzyme. 3.9°C increase in Tm-value compared to wild-type enzyme Homo sapiens
T245P/T283M all of the TyrH is insoluble and no enzyme can be purified Homo sapiens
T283M 1.2fold decrease in Km-value for L-tyrosine compared to wild-type enzyme, 1.2fold decrease in Ki-value for L-tyrosine compared to wild-type enzyme, 1.3fold decrease in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 4.2fold decrease of turnover-number compared to wild-type enzyme Homo sapiens
T463M 1.1fold decrease in Km-value for L-tyrosine compared to wild-type enzyme, Ki-value for L-tyrosine is nearly identical to wild-type value compared to wild-type enzyme, 1.4fold decrease in KM-value for tetrahydrobiopterin compared to wild-type enzyme, 1.2fold increase of turnover-number compared to wild-type enzyme. 7.7°C increase in Tm-value compared to wild-type enzyme Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
L-tyrosine
-
Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.009
-
tetrahydrobiopterin pH 7.0, 30°C, mutant enzyme T463M Homo sapiens
0.01
-
tetrahydrobiopterin pH 7.0, 30°C, mutant enzyme R306H Homo sapiens
0.01
-
tetrahydrobiopterin pH 7.0, 30°C, mutant enzyme T283M Homo sapiens
0.013
-
tetrahydrobiopterin pH 7.0, 30°C, wild-type enzyme Homo sapiens
0.014
-
tetrahydrobiopterin pH 7.0, 30°C, mutant enzyme T245P Homo sapiens
0.039
-
L-tyrosine pH 7.0, 30°C, mutant enzyme T283M Homo sapiens
0.042
-
L-tyrosine pH 7.0, 30°C, mutant enzyme R306H Homo sapiens
0.043
-
L-tyrosine pH 7.0, 30°C, mutant enzyme T463M Homo sapiens
0.046
-
L-tyrosine pH 7.0, 30°C, wild-type enzyme Homo sapiens
0.066
-
L-tyrosine pH 7.0, 30°C, mutant enzyme T245P Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
inclusion body mutant enzymes T283M and R306H expressed in Escherichia coli are mainly found in inclusion bodies but a small amount of soluble enzyme is produced Homo sapiens 16234
-
soluble mutant enzyme T245P and T463 M expressed in Escherichia coli are predominantly soluble. Mutant enzymes T283M and R306H expressed in Escherichia coli are mainly found in inclusion bodies but a small amount of soluble enzyme is produced Homo sapiens
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens the enzyme catalyzes the rate-limiting step in the biosynthesis of dopmaine. The physiological effects of the mutations described in cases of autosomal recessive DOPA-responsive dystonia are primarily due to the decreased stability of the mutant proteins razher than decreases in their intrinsic activities ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens

Storage Stability

Storage Stability Organism
-80°C, purified wild-type enzyme can be stored indefinetely in absence of glycerol. the mutant enzymes T245P and T463M behave similarly. The removal of glyceryl from the T283M and R306H enzymes results in significant precipitation and loss of the protein Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-tyrosine + tetrahydrobiopterin + O2
-
Homo sapiens 3,4-dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin + H2O
-
?
additional information the enzyme catalyzes the rate-limiting step in the biosynthesis of dopmaine. The physiological effects of the mutations described in cases of autosomal recessive DOPA-responsive dystonia are primarily due to the decreased stability of the mutant proteins razher than decreases in their intrinsic activities Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
TyrH
-
Homo sapiens
tyrosine hydroxylase
-
Homo sapiens

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
41
-
Tm-value of mutant enzyme T463M is 44.3°C Homo sapiens
44
-
Tm-value of mutant enzyme T245P is 44.3°C Homo sapiens
46
-
Tm-value of mutant enzyme R306H is 45.8°C Homo sapiens
48
-
Tm-value of wild-type enzyme is 48.2°C Homo sapiens
50
-
50% loss of activity after 90 min, 80% loss of activity after 2 h, wild-type enzyme Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.8
-
L-tyrosine pH 7.0, 30°C, mutant enzyme T283M Homo sapiens
3.33
-
L-tyrosine pH 7.0, 30°C, wild-type enzyme Homo sapiens
3.68
-
L-tyrosine pH 7.0, 30°C, mutant enzyme R306H Homo sapiens
3.87
-
L-tyrosine pH 7.0, 30°C, mutant enzyme T463M Homo sapiens
5.35
-
L-tyrosine pH 7.0, 30°C, mutant enzyme T245P Homo sapiens

Cofactor

Cofactor Comment Organism Structure
tetrahydrobiopterin
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.037
-
L-tyrosine pH 7.0, 30°C, mutant enzyme T283M Homo sapiens
0.044
-
L-tyrosine pH 7.0, 30°C, mutant enzyme T463M Homo sapiens
0.046
-
L-tyrosine pH 7.0, 30°C, wild-type enzyme Homo sapiens
0.048
-
L-tyrosine pH 7.0, 30°C, mutant enzyme R306H Homo sapiens
0.073
-
L-tyrosine pH 7.0, 30°C, mutant enzyme T245P Homo sapiens