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Information on EC 1.8.4.9 - adenylyl-sulfate reductase (glutathione)
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1.8.4.9 adenylyl-sulfate reductase (glutathione)IUBMB Comments
This enzyme differs from EC 1.8.99.2, adenylyl-sulfate reductase, in using glutathione as the reductant. Glutathione can be replaced by gamma-glutamylcysteine or dithiothreitol, but not by thioredoxin, glutaredoxin or 2-sulfanylethan-1-ol (2-mercaptoethanol). The enzyme from the mouseear cress, Arabidopsis thaliana, contains a glutaredoxin-like domain. The enzyme is also found in other photosynthetic eukaryotes, e.g., the Madagascar periwinkle, Catharanthus roseus and the hollow green seaweed, Ulva intestinalis.
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Word Map
- 1.8.4.9
-
dissimilatory
- thiosulfate
-
sulfate-reducing
-
sulfurylase
-
sulfur-oxidizing
- thioparus
-
qmoabc
The enzyme appears in viruses and cellular organisms
Synonyms
adenosine-5'-phosphosulfate reductase, apr1p, eiapr, adenosine-5'-phosphosulphate reductase, adenosine 5-phosphosulfate reductase, ppapr-b, prh-19, prh-26, prh-43, atapr1, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3'-phosphoadenosine-5'-phosphosulfate reductase homolog 19
-
-
-
-
3'-phosphoadenosine-5'-phosphosulfate reductase homolog 26
-
-
-
-
3'-phosphoadenosine-5'-phosphosulfate reductase homolog 43
-
-
-
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5'-adenylylsulfate reductase
adenosine 5'-phosphosulfate reductase
adenosine 5-phosphosulfate reductase
adenosine-5'-phosphosulphate reductase
APR
APR2
APS reductase
PAPS reductase homolog 19
-
-
-
-
PAPS reductase homolog 26
-
-
-
-
PAPS reductase homolog 43
-
-
-
-
plant-type 5'-adenylylsulfate reductase
Prh-19
-
-
-
-
Prh-26
-
-
-
-
Prh-43
-
-
-
-
additional information
enzyme belongs to the thioredoxin superfamily
5'-adenylylsulfate reductase
-
-
-
-
APR
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-
-
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APS reductase
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-
-
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plant-type 5'-adenylylsulfate reductase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
AMP + sulfite + glutathione disulfide = adenylyl sulfate + 2 glutathione
-
-
-
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AMP + sulfite + glutathione disulfide = adenylyl sulfate + 2 glutathione
the reaction catalyzed by APR can be divided into three steps. In the first step, APS binds to the protein, and a reductive transfer results in sulfite bound to the active-site cysteine in a stable reaction intermediate. In the second step, free sulfite is released by the action of the C-terminal domain. In the third step, the glutaredoxin active site is regenerated by reduction with GSH reductase
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
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redox reaction
-
-
-
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reduction
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
AMP,sulfite:glutathione-disulfide oxidoreductase (adenosine-5'-phosphosulfate-forming)
This enzyme differs from EC 1.8.99.2, adenylyl-sulfate reductase, in using glutathione as the reductant. Glutathione can be replaced by gamma-glutamylcysteine or dithiothreitol, but not by thioredoxin, glutaredoxin or 2-sulfanylethan-1-ol (2-mercaptoethanol). The enzyme from the mouseear cress, Arabidopsis thaliana, contains a glutaredoxin-like domain. The enzyme is also found in other photosynthetic eukaryotes, e.g., the Madagascar periwinkle, Catharanthus roseus and the hollow green seaweed, Ulva intestinalis.
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CAS REGISTRY NUMBER
COMMENTARY
9027-75-2
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenosine 5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
-
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-bisphosphate + sulfite + oxidized glutathione
-
-
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
5'-adenylyl sulfate + thioredoxin
AMP + sulfite + thioredoxin disulfide
-
recombinant enzyme in transgenic Arabidopsis thaliana plants
-
-
?
5'-adenylylsulfate + dithioerythritol
adenosine 5'-monophosphate + sulfite + oxidized dithioerythritol
5'-adenylylsulfate + dithiothreitol
adenosine 5'-monophosphate + sulfite + oxidized dithiothreitol
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
5'-adenylylsulfate + glutathione + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
adenosine 5'-phosphosulfate + glutathione
?
-
PpAPR-B is much more active with adenosine 5'-phosphosulfate as a substrate than with 3'-phosphoadenosine 5'-phosphosulfate
-
-
?
AMP + sulfite + glutathione disulfide
adenylyl sulfate + 2 glutathione
-
-
-
?
cystine + glutathione
cysteine + glutathione disulfide
catalyzed by the holoenzyme APR1p and the C-domain
-
-
?
dehydroascorbate + glutathione
ascorbate + glutathione disulfide
catalyzed by the holoenzyme APR1p and the C-domain
-
-
?
hydroxyethyldisulfide + glutathione
?
catalyzed by the holoenzyme APR1p and the C-domain
-
-
?
insulin disulfide + glutathione
insulin + glutathione disulfide
catalyzed by the C-domain, not by the holoenzyme APR1p or the R-domain
-
-
?
oxidized ribonucleotide reductase + glutathione
reduced ribonucleotide reductase + glutathione disulfide
catalyzed by the C-domain, not by the holoenzyme APR1p or the R-domain
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
-
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
50fold lower activity than with 5'-adenylylsulfate
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
no activity with 3'-phosphoadenosine-5'-phosphosulfate
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
no activity with 3'-phosphoadenosine-5'-phosphosulfate
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
no activity with 3'-phosphoadenosine-5'-phosphosulfate
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
no activity with 3'-phosphoadenosine-5'-phosphosulfate
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
no activity with 3'-phosphoadenosine-5'-phosphosulfate
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
no activity with 3'-phosphoadenosine-5'-phosphosulfate
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
no activity with 3'-phosphoadenosine-5'-phosphosulfate
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
no activity with 3'-phosphoadenosine-5'-phosphosulfate
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
no activity with 3'-phosphoadenosine-5'-phosphosulfate
-
-
?
3'-phosphoadenosine-5'-phosphosulfate + glutathione
adenosine 3',5'-diphosphate + sulfite + oxidized glutathione
-
no activity with 3'-phosphoadenosine-5'-phosphosulfate
-
-
?
5'-adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
5'-adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
enzyme is involved in reductive sulfate assimilation, pathway overview
-
-
?
5'-adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
catalyzed by the holoenzyme APR1p, not by the C-domain
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-
?
5'-adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
5'-adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
5'-adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
enzyme is involved in reductive sulfate assimilation, pathway overview
-
-
?
5'-adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
5'-adenylylsulfate + dithioerythritol
adenosine 5'-monophosphate + sulfite + oxidized dithioerythritol
-
-
-
-
?
5'-adenylylsulfate + dithioerythritol
adenosine 5'-monophosphate + sulfite + oxidized dithioerythritol
-
-
-
-
?
5'-adenylylsulfate + dithiothreitol
adenosine 5'-monophosphate + sulfite + oxidized dithiothreitol
-
-
-
-
?
5'-adenylylsulfate + dithiothreitol
adenosine 5'-monophosphate + sulfite + oxidized dithiothreitol
-
-
-
-
ir
5'-adenylylsulfate + dithiothreitol
adenosine 5'-monophosphate + sulfite + oxidized dithiothreitol
-
-
-
-
?
5'-adenylylsulfate + dithiothreitol
adenosine 5'-monophosphate + sulfite + oxidized dithiothreitol
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
?
5'-adenylylsulfate + glutathione + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
r
5'-adenylylsulfate + glutathione + glutathione
adenosine monophosphate + sulfite + oxidized glutathione
-
-
-
-
r
adenylyl sulfate + 2 glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
adenylyl sulfate + 2 glutathione
AMP + sulfite + glutathione disulfide
-
-
-
?
adenylyl sulfate + 2 glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
adenylyl sulfate + 2 glutathione
AMP + sulfite + glutathione disulfide
-
-
-
?
adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
sulfate assimilation pathway in Physcomitrella patens, overview
-
-
?
adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
substrate binding structure, modelling, overview
-
-
?
additional information
?
-
enzyme is involved in sulfate assimilation
-
-
?
additional information
?
-
-
enzyme is involved in sulfate assimilation
-
-
?
additional information
?
-
-
APR is the key enzyme of sulfate assimilation, extensive posttranscriptional regulation of plant APR, e.g. by salt stress, sulfate assimilation pathway is controlled by a complex network of multiple signals on different regulatory levels, overview
-
-
?
additional information
?
-
GSH is docked into the AtAPR1 redox domain active site by manual docking, superimposing the structures of glutaredoxin bound with GSH on that of the AtAPR1 redox domain. The structure of cGrx1 complexed with GSH (PDB code 4TR1) is used as a template. Interaction between GSH and the AtAPR1 redox domain is analyzed, binding structure analysis, overview
-
-
-
additional information
?
-
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the moss Physcomitrella patens is unique among these organisms in possessing orthologs of both APR and PAPR, EC 1.8.4.8, genes
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
5'-adenylyl sulfate + thioredoxin
AMP + sulfite + thioredoxin disulfide
-
recombinant enzyme in transgenic Arabidopsis thaliana plants
-
-
?
AMP + sulfite + glutathione disulfide
adenylyl sulfate + 2 glutathione
-
-
-
?
5'-adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
enzyme is involved in reductive sulfate assimilation, pathway overview
-
-
?
5'-adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
enzyme is involved in reductive sulfate assimilation, pathway overview
-
-
?
adenylyl sulfate + 2 glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
adenylyl sulfate + 2 glutathione
AMP + sulfite + glutathione disulfide
-
-
-
?
adenylyl sulfate + 2 glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
adenylyl sulfate + 2 glutathione
AMP + sulfite + glutathione disulfide
-
-
-
?
adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
-
-
-
?
adenylyl sulfate + glutathione
AMP + sulfite + glutathione disulfide
-
sulfate assimilation pathway in Physcomitrella patens, overview
-
-
?
additional information
?
-
enzyme is involved in sulfate assimilation
-
-
?
additional information
?
-
-
enzyme is involved in sulfate assimilation
-
-
?
additional information
?
-
-
APR is the key enzyme of sulfate assimilation, extensive posttranscriptional regulation of plant APR, e.g. by salt stress, sulfate assimilation pathway is controlled by a complex network of multiple signals on different regulatory levels, overview
-
-
?
additional information
?
-
-
the moss Physcomitrella patens is unique among these organisms in possessing orthologs of both APR and PAPR, EC 1.8.4.8, genes
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
glutathione
dependent on, specific cofactor for the carboxyterminal glutathione-dependent reductase domain of the enzyme, can be exchanged for equally active DTT, glutathione is slightly inhibitory at high concentrations
thioredoxin
-
recombinant enzyme utilizes the plant thioredoxins m and f in transgenic plants
additional information
DTT can be exchanged for glutathione, equally active
-
additional information
-
DTT can be exchanged for glutathione, equally active
-
additional information
no activity with 2-mercaptoethanol, gamma-glutamylcysteine, or cysteine
-
additional information
-
no activity with 2-mercaptoethanol, gamma-glutamylcysteine, or cysteine
-
additional information
-
FeS cluster as a cofactor in PpAPR, no activity with thioredoxin
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
(NH4)2SO4
Fe2+
Mg2+
NaCl
-
all three APR isoforms increased 3fold in roots after 5 h of treatment with 150 mM NaCl, regulation of salt stress by plant hormone signalling, overview
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
adenosine 5'-phosphosulfate
-
inhibits activity with 3'-phosphoadenosine 5'-phosphosulfate
KNO3
-
abolishes enzyme activation by other salts and inhibits the enzyme
5'-adenylylsulfate
-
when thioredoxin concentrations are limiting, elevated concentrations of APS result in inhibition
adenosine-5'-phosphate
-
competitive inhibition, Ki of 0.34 mM with 10 mM glutathione
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
DTT
-
DTT can replace glutathione as reductant, 5 mM DTT increases activity 40fold
additional information
-
feeding of O-acetylserine leads to increased accumulation of sulfite and thiosulfate in wild-type plants
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Tuberculosis
Crystal Structure of the [4Fe-4S] Cluster-Containing Adenosine-5'-phosphosulfate Reductase from Mycobacterium tuberculosis.
Tuberculosis
Identification of critical ligand binding determinants in Mycobacterium tuberculosis adenosine-5'-phosphosulfate reductase.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.031
3'-phosphoadenosine-5'-phosphosulfate
-
assay conditions: APS reductase (0.0009 mM), EST (0.10 unit/ml), thioredoxin (0.037 mM), MgCl2 (3.0 mM), DTT (2.0 mM), pNPS (10 mM), GSH (5.0 mM), and Hepes (50 mM, pH 8.0), at 25°C
additional information
additional information
thermodynamic parameters for binding of AtAPR1 redox domain to GSH or GSSG
-
0.00057
5'-adenylylsulfate
-
assay conditions: APS reductase (0.00021 mM), PK (8.4 units/ml), LDH (18.0 units/ml), adenylate kinase (10 units/ml), thioredoxin (0.0373 mM), MgCl2 (3.0 mM), DTT (2.0 mM), ATP (1.0 mM), PEP (1.0 mM), EDTA (1.0 mM), GSH (5.0 mM), NADH (0.030 mM), and Hepes (50 mM, pH 8.0), at 25°C
0.6
glutathione
holoenzyme APR1p with substrate 5'-adenylyl sulfate, pH 8.5, 30°C
1.12
glutathione
about, holoenzyme APR1p and C-domain with substrates hydroxyethyldisulfide, or cystine, pH 8.0, 24°C
1.15
glutathione
about, holoenzyme APR1p and C-domain with substrate dehydroascorbate, pH 6.9, 24°C
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.012
3'-phosphoadenosine-5'-phosphosulfate
-
assay conditions: APS reductase (0.0009 mM), EST (0.10 unit/ml), thioredoxin (0.037 mM), MgCl2 (3.0 mM), DTT (2.0 mM), pNPS (10 mM), GSH (5.0 mM), and Hepes (50 mM, pH 8.0), at 25°C
0.153
5'-adenylylsulfate
-
assay conditions: APS reductase (0.00021 mM), PK (8.4 units/ml), LDH (18.0 units/ml), adenylate kinase (10 units/ml), thioredoxin (0.0373 mM), MgCl2 (3.0 mM), DTT (2.0 mM), ATP (1.0 mM), PEP (1.0 mM), EDTA (1.0 mM), GSH (5.0 mM), NADH (0.030 mM), and Hepes (50 mM, pH 8.0), at 25°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000002
-
with 3'-phosphoadenosine 5'-phosphosulfate as substrate and 5 mM DTT, recombinant protein expressed in Escherichia coli
0.000007
-
with 3'-phosphoadenosine 5'-phosphosulfate as substrate and 5 mM DTT, recombinant protein expressed in Escherichia coli
0.00022
-
with 5'-adenylylsulfate as substrate and 5 mM DTT, recombinant protein expressed in Escherichia coli
0.00059
-
with 5'-adenylylsulfate as substrate and 5 mM DTT, recombinant protein expressed in Escherichia coli
0.0023 - 0.006
0.013
-
after purification of His-tagged protein with Nickel-affinity chromatography
0.1 - 0.25
additional information
0.0023 - 0.006
-
transgenic plants with the recombinant Pseudomonas aeruginosa enzyme utilizing thioredoxin
0.0023 - 0.006
-
recombinant enzyme in transgenic Arabidopsis thaliana plants, cofactor thioredoxin