Information on EC 1.3.1.12 - prephenate dehydrogenase

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

EC NUMBER
COMMENTARY hide
1.3.1.12
-
RECOMMENDED NAME
GeneOntology No.
prephenate dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
prephenate + NAD+ = 4-hydroxyphenylpyruvate + CO2 + NADH
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
-
-
-
-
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
3-dimethylallyl-4-hydroxybenzoate biosynthesis
-
-
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
L-tyrosine biosynthesis I
-
-
Metabolic pathways
-
-
Novobiocin biosynthesis
-
-
Phenylalanine, tyrosine and tryptophan biosynthesis
-
-
tyrosine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
prephenate:NAD+ oxidoreductase (decarboxylating)
This enzyme in the enteric bacteria also possesses chorismate mutase activity (EC 5.4.99.5 chorismate mutase) and converts chorismate into prephenate.
CAS REGISTRY NUMBER
COMMENTARY hide
9044-92-2
-
9044-92-2
prephenate dehydrogenase
94859-19-5
hydroxyphenylpyruvate synthase: chorismate mutase-prephenate dehydrogenase bifunctional enzyme
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
JA1
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Escherichia coli K-12 MG1655
strain K-12 MG1655
-
-
Manually annotated by BRENDA team
strain H37Rv
-
-
Manually annotated by BRENDA team
strain H37Rv
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
pt MN64
-
-
Manually annotated by BRENDA team
no activity in Actinomycetales
-
-
-
Manually annotated by BRENDA team
no activity in coryneform bacteria
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Soil bacterium
uncultured alkaline-polluted bacterium
UniProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-arogenate + NAD+
L-tyrosine + NADH + CO2
show the reaction diagram
prephenate + NAD+
4-hydroxyphenylpyruvate + CO2 + NADH
show the reaction diagram
prephenate + NAD+
4-hydroxyphenylpyruvate + CO2 + NADH + H+
show the reaction diagram
prephenate + NAD+
4-hydroxyphenylpyruvate + NADH + CO2
show the reaction diagram
prephenate + NAD+
4-hydroxyphenylpyruvate + NADH + H+ + CO2
show the reaction diagram
prephenate + NADP+
4-hydroxyphenylpyruvate + NADPH + CO2
show the reaction diagram
-
-
-
-
?
additional information
?
-
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
prephenate + NAD+
4-hydroxyphenylpyruvate + CO2 + NADH
show the reaction diagram
prephenate + NAD+
4-hydroxyphenylpyruvate + CO2 + NADH + H+
show the reaction diagram
prephenate + NAD+
4-hydroxyphenylpyruvate + NADH + CO2
show the reaction diagram
prephenate + NAD+
4-hydroxyphenylpyruvate + NADH + H+ + CO2
show the reaction diagram
Soil bacterium
J9XQS6
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cu2+
Soil bacterium
0.5 mM, 56.8% residual activity
Fe3+
Soil bacterium
0.5 mM, 58.7% residual activity
KCl
-
required for optimal activity
Mn2+
Soil bacterium
0.5 mM, 72% residual activity
SDS
Soil bacterium
0.10%, 18.3% residual activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-hydroxyphenylacetate
-
-
4-hydroxymercuribenzoate
4-hydroxyphenylpyruvate
5,5'-dithiobis(2-nitrobenzoate)
-
-
5,6-dihydro-5,6-dihydroxychorismate
-
-
adamantane analogues
-
-
-
adamantane-1,3-diacetate
-
-
adamantane-1-acetate
-
-
adamantane-1-carboxylate
-
-
adamantane-1-phosphonate
-
-
alpha-Methyl-D,L-tyrosine
-
-
chorismate
-
-
chorismate analogues
-
-
-
chorismate-5,6-epoxide
-
-
citrate
-
-
Co2+
-
weakly inhibits
coumaric acid
-
-
D-tyrosine
-
-
Diethylmalonate
-
-
dihydroxyphenylalanine
-
-
iodoacetamide
iodoacetate
L-phenylalanine
-
-
L-tryptophan
-
-
L-Tyr
-
L-Tyr inhibits TyrAp activity by 90% at concentrations higher than 0.5 mM
L-tyrosine
malonate
-
-
N-benzenesulfonyl-L-phenylalanine
-
-
-
N-Benzyloxycarbonyl-L-phenylalanine
-
-
N-bromosuccinimide
-
-
N-ethylmaleimide
-
-
N-Toluene-p-sulfonyl-L-p-aminophenylalanine
-
-
N-Toluene-p-sulfonyl-L-phenylalanine
-
-
NaCl
-
IC50: 0.01 mM
Tetranitromethane
-
-
trans-2,3-pleiadanedicarboxylic acid
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i.e. diacid, 50% inhibition at 0.25 mM, inhibits competitively the prephenate dehydrogenase activity, but not the chorismate mutase activity of the enzyme
tyrosine
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Adamantane 1-acetate
-
-
bovine serum albumin
Guanidine-HCl
-
activates at low concentrations, at higher concentrations concomitant loss of activity with a multi-state pathway of denaturation
L-tryptophan
-
-
L-tryptophan analogues
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methylated or fluorinated
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phenylalanine
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.017 - 0.249
L-arogenate
0.01 - 3.7
NAD+
0.017 - 5
prephenate
additional information
additional information
-
Km of enzyme fragments
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.3 - 68
L-arogenate
0.0000583 - 356.1
NAD+
0.00005 - 170.4
prephenate
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2
NAD+
Streptococcus mutans
-
pH 6.8, 37C
7
11.6 - 880
prephenate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.17
2-hydroxyphenylacetate
-
pH 7.8, 37C
0.13 - 0.4
4-hydroxyphenylpyruvate
0.11
5,6-dihydro-5,6-dihydroxychorismate
-
pH 7.8, 37C
0.15
adamantane-1,3-diacetate
-
pH 7.8, 37C
0.13
adamantane-1-acetate
-
pH 7.8, 37C
0.31
adamantane-1-carboxylate
-
pH 7.8, 37C
0.14
adamantane-1-phosphonate
-
pH 7.8, 37C
0.13
chorismate-5,6-epoxide
-
pH 7.8, 37C
0.2
coumaric acid
-
-
1.3
D-tyrosine
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-
0.47
dihydroxyphenylalanine
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-
0.3
L-phenylalanine
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-
0.7
L-tryptophan
-
-
0.003 - 5.5
L-tyrosine
0.21
trans-2,3-pleiadanedicarboxylic acid
-
pH 7.8, 37C
0.0159 - 0.37
tyrosine
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
NaCl
Mycobacterium tuberculosis
-
IC50: 0.01 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
12.6
-
pH 6.8, 37C
25.2
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purified recombinant enzyme fragment comprising amino acid residues 93-373
33
-
chorismate mutase-prephenate dehydrogenase bifunctional enzyme
55
-
purified recombinant enzyme fragment comprising amino acid residues 96-373
98
-
purified recombinant wild-type enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8.5
Soil bacterium
more than 75% of maximum activity within
8
-
50% of maximum activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30 - 40
-
assay at 37C
45
Soil bacterium
-
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 55
-
not active at 65C
35 - 50
Soil bacterium
more than 80% of maximum activity within
37
-
decrease of activity above
45 - 95
-
-
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5
Soil bacterium
-
PDB
SCOP
CATH
ORGANISM
UNIPROT
Aquifex aeolicus (strain VF5)
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Streptococcus mutans serotype c (strain ATCC 700610 / UA159)
Streptococcus thermophilus (strain ATCC BAA-250 / LMG 18311)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
31000
-
sequence analysis
36420
-
MALDI-TOF studies of the recombinant His-rMtPDH
42040
-
calculated from nucleotide sequence
52500
-
calculated from nucleotide sequence
55000 - 65000
-
gel filtration, gel electrophoresis, sucrose density gradient centrifugation
66000
-
gel filtration
68000
-
gel filtration
75000
-
gel filtration
76000 - 81000
-
chorismate mutase-prephenate dehydrogenase bifunctional enzyme, gel filtration, gel electrophoresis
78000 - 100000
140000
-
gel filtration
150000
-
gel filtation
420000
gel filtration
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
Soil bacterium
x * 31400, calculated
heterodimer
-
1 * 37000 + 1 * 34000, SDS-PAGE
homohexamer
6 * 66000, SDS-PAGE; 6 * 70946, calculated from sequence
additional information
-
MW of recombinant enzyme fragments, overview, structural localization of the different enzyme activities on the enzyme molecule
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
proteolytic digestion of recombinant wild-type enzyme by papain, pH 6.8, 37C
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with NAD+, by hanging drop vapor diffusion technique at room temperature, one modified nucleotide-binding domain and a novel helical prephenate binding domain, active site formed at the domain interface and shared between the subunits of the dimer, access to active site may be regulated via a gated mechanism, modulated by an ionic network involving a conserved arginine, active site residues include Ser126 and Lys246 and the catalytic His147, two functional domains of chorismate mutase-prephenate dehydrogenase are interdependent
-
prephenate dehydrogenase bound with NAD+ plus either 4-hydroxyphenylpyuvate, 4-hydroxyphenylpropionate, or L-tyrosine. Resiudes His147 and Arg250 are key catalytic and binding groups, respectively, and Ser126 participates in both catalysis and substrate binding through the ligand 4-hydroxyl group. Inhibitor tyrosine binds directly to the active site of the enzyme and not to an allosteric site
prephenate dehydrogenase component of the TyrA protein from strain Rd KW20 in complex with inhibitor tyrosine and cofactor NAD+, sitting drop vapour diffusion method, 200 nl of 19.6 mg/ml protein in 20 mM HEPES pH 8.0, 200 mM NaCl, 40 mM imidazole, 1 mM TCEP are mixed with 200 nl reservoir solution containing 0.04 M potassium dihydrogen phosphate, 20.0% v/v glycerol and 16.0% w/v PEG 8000, X-ray diffrraction structure determination and analysis at 2.0 A resolution
to 2.1 A resolution. The N-terminal alpha/beta domain has a Rossman fold for binding a NAD+ molecule. The C-terminal domain adopts a helical architecture and is involved in homo-dimerization. NAD+ binding stabilizes the active site and facilitates the substrate, prephenate, binding
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
bovine serum albumin, bovine casein or prephenate stabilizes
-
citrate stabilizes
-
dialysis inactivates
dithiothreitol stabilizes
-
EDTA stabilizes
-
glycerol stabilizes
NAD+ plus tyrosine stabilizes
-
purified enzyme and diluted solution is unstable
-
stability in Tris-HCl buffer higher than in phosphate buffer
thiols stabilize
-
tyrosine stabilizes
unstable in buffers of low ionic strength lacking glycerol
-
unstable in crude extracts
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, 0.02% sodium azide, N2-atmosphere, more than 0.1 mg/ml protein
-
-20C, 0.1 M N-ethylmorpholine, pH 7.0, 21 mM citrate, 10% v/v glycerol, 1 mM EDTA, 1 mM DTT
-
-20C, 0.1 M Tris-HCl buffer, pH 7.5, 1 mM EDTA, 1 mM DTT, 1 mM tyrosine, 70% w/v ammonium sulfate, several weeks
-
-20C, 50 mM Cl/N-ethylmorpholine pH 7.2, 1 mM EDTA, 1 mM sodium citrate, 0.02% w/v sodium azide, 50% v/v glycerol, 10 mM DTT, N2-atmosphere, at least 3 months
-
-20C, 50 mM phosphate buffer, pH 7.4, at least 0.7 mg/ml protein, 10 months
-
-80C, purified recombinant His-tagged wild-type enzyme, complete loss of activity when stored in 0.1 M sodium citrate, pH 7.5, 10% glycerol, 1 mM DTT, or moderate loss in activity when stored in 0.1 M MES, pH 7.5, 0.051 M N-ethylmorpholine, 0.01 M diethanolamine, 1 mM EDTA, 1 mM DTT, 10% glycerol,
-
0-4C, 0.1 M Tris-HCl buffer, pH 7.5, 1 mM EDTA, 1 mM DTT, 1 mM tyrosine, 70% w/v ammonium sulfate, for at least 10 days
-
4C, -20C, or -80C, 50 mM Tris, 25% glycerol, no significant differences in activity, even after one month of storage
-
4C, 0.1 M N-ethylmorpholine, pH 7.0, 21 mM citrate, 10% v/v glycerol, 1 mM EDTA, 1 mM DTT, up to 4 weeks
-
4C, 0.1 M phosphate buffer pH 7.6, over-night, complete loss of activity
-
4C, ammonium sulfate precipitate
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by Ni-NTA column
-
by nickel-affinity chromatography
-
chorismate mutase-prephenate dehydrogenase bifunctional enzyme
chorismate mutase-prephenate dehydrogenase bifunctional enzyme; one-step procedure by affinity chromatography
-
chorismate mutase-prephenate dehydrogenase bifunctional enzyme; partial
chorismate mutase-prephenate dehydrogenase bifunctional enzyme; wild-type and mutant enzyme
-
copurification with arogenate dehydrogenase
-
copurification with arogenate dehydrogenase; partial
-
copurification with pretyrosine dehydrogenase
-
His-rMtPDH, to near homogeneity by Ni-NTA affinity chromatography, ca. 94% pure
-
His6-tagged proteins, to homogeneity by gel filtration
-
not associated with other enzymatic activities
-
recombinant enzyme
Soil bacterium
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography, cleavage of the tag by TEV protease
recombinant His-tagged wild-type enzyme and enzyme fragments
-
recombinant protein
-
together with arogenate dehydrogenase
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expression in Escherichia coli
expression of His-tagged enzyme in Escherichia coli
gene tyrA, genetic mapping of chorismate mutase and prephenate dehydrogenase activity, expression of the wild-type enzyme, the 2 activity domains, and gene fragments exhibiting either chorismate mutase or prephenate dehydrogenase activity as His-tagged proteins and peptides in strain BL21(DE3), respectively
-
genetic separability of chorismate mutase and prephenate dehydrogenase in Escherichia coli
-
into tyrA-pET30a and expressed in Escherichia coli BL21(DE3) as His-rMtPDH
-
into vector pET-15b, expression as His-tagged protein in Escherichia coli
-
into vector pET15b and expressed in Escherichia coli BL21-Gold (DE3)
-
monofunctional prephenate dehydrogenase, expressed in Escherichia coli
-
mutants cloned into pZE21-MCS1 and transformed to Escherichia coli DH5alpha, wild-type and mutants subcloned into vector pET-30XA/LIC and expressed in Escherichia coli BL21(DE3)
-
overexpressed in Escherichia coli
overexpression
-
T7 expression system
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DELTA1-19
-
delta19PD, more sensitive to temperature effects yielding a half-life of 55 min at 95C versus 2 h for PD
H147N
inactive, binds prephenate with apparent affinity similar to wild-type
H217A
40fold increase in Km for prephenate, no inhibition by tyrosine
H217N
30fold increase in Km for prephenate, no inhibition by tyrosine
R250Q
10fold increase in the Km for prephenate and a 20fold increase in Ki for tyrosine
S126A
15fold reduction in kcat, a 10fold increase in the Km value for prephenate, and a 2-fold increase in Ki for tyrosine
H131A
-
chorismate mutase-prephenate dehydrogenase bifunctional enzyme, mutant enzyme retains 10% of dehydrogenase activity and 30% mutase activity compared to the wild-type enzyme, His131 is not an essential residue whose protonation state is critical for catalysis or substrate binding
H189N
-
chorismate mutase-prephenate dehydrogenase bifunctional enzyme, mutant enzyme shows less than 0.01% the activity of wild-type mutase and dehydrogenase
H197N
-
chorismate mutase-prephenate dehydrogenase bifunctional enzyme, mutant enzyme exhibits no significant dehydrogenase activity, retains nearly wild-type mutase activity and unaltered Michaelis constants for chorismate, prephenate and NAD+
K37A
-
chorismate mutase-prephenate dehydrogenase bifunctional enzyme, mutant protein poorly expressed, no detectable mutase or dehydrogenase activity, structural changes may result in its inactivity and instability
K37Q
-
chorismate mutase-prephenate dehydrogenase bifunctional enzyme, mutant enzyme exhibits no mutase activity while retaining wild-type dehydrogenase activity
R294Q
-
chorismate mutase-prephenate dehydrogenase bifunctional enzyme, R294Q substitution reduces the affinity of the enzyme for prephenate, Arg294 interacts electrostatically with the ring carboxylate at C1 of prephenate
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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