BRENDA - Enzyme Database
show all sequences of 1.1.1.169

Crystal structure of archaeal ketopantoate reductase complexed with coenzyme a and 2-oxopantoate provides structural insights into feedback regulation

Aikawa, Y.; Nishitani, Y.; Tomita, H.; Atomi, H.; Miki, K.; Proteins 84, 374-382 (2016)

Data extracted from this reference:

Cloned(Commentary)
Cloned (Commentary)
Organism
gene TK1968, sequence comparisons, recombinant expression of wild-type and mutant enzymes in Escherichia coli strain Rosetta2 (DE3) pLysS
Thermococcus kodakarensis
Crystallization (Commentary)
Crystallization (Commentary)
Organism
purified enzyme in complex with CoA and 2-oxopantoate, hanging drop vapor diffusion method, mixing of 0.001 ml of 10 mg/ml protein and 1 mM CoA and 1 mM 2-oxopantoate with 0.001 ml of reservoir solution containing 100 mM Na acetate, pH 4.5, 20-25% v/v 2-methyl-2,4-pentanediol, and equilibration against 0.5 ml of reservoir solution, at 20°C, 3 days, X-ray diffraction structure determination and analysis at 1.65 A resolution, modeling by molecular replacement method using N-terminal (1-165 residues) and C-terminal (171-309 residues) domains of Ec-KPR structure, PDB ID 2OFP, as separated search models, respectively
Thermococcus kodakarensis
Engineering
Protein Variants
Commentary
Organism
C84A
site-directed mutagenesis, crystal structure analysis, overview
Thermococcus kodakarensis
Inhibitors
Inhibitors
Commentary
Organism
Structure
CoA
feedback inhibition, competitive with NADPH, the binding sites of CoA and NADP+ overlap, explaining the competitive manner of inhibition by CoA, binding structure analysis, overview
Thermococcus kodakarensis
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ID
(R)-pantoate + NADP+
Thermococcus kodakarensis
-
2-dehydropantoate + NADPH + H+
-
-
r
(R)-pantoate + NADP+
Thermococcus kodakarensis ATCC BAA-918
-
2-dehydropantoate + NADPH + H+
-
-
r
Organism
Organism
UniProt
Commentary
Textmining
Thermococcus kodakarensis
Q5JGC2
-
-
Thermococcus kodakarensis ATCC BAA-918
Q5JGC2
-
-
Purification (Commentary)
Purification (Commentary)
Organism
recombinant wild-type and mutant enzymes from Escherichia coli strain Rosetta2 (DE3) pLysS by nickel affinity chromatography, avidin affinity chromatography, and dialysis
Thermococcus kodakarensis
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
Substrate Product ID
(R)-pantoate + NADP+
-
741385
Thermococcus kodakarensis
2-dehydropantoate + NADPH + H+
-
-
-
r
(R)-pantoate + NADP+
substrate binding structure analysis, overview
741385
Thermococcus kodakarensis
2-dehydropantoate + NADPH + H+
-
-
-
r
(R)-pantoate + NADP+
-
741385
Thermococcus kodakarensis ATCC BAA-918
2-dehydropantoate + NADPH + H+
-
-
-
r
(R)-pantoate + NADP+
substrate binding structure analysis, overview
741385
Thermococcus kodakarensis ATCC BAA-918
2-dehydropantoate + NADPH + H+
-
-
-
r
Subunits
Subunits
Commentary
Organism
More
enzyme structure analysis and comparisons, overview
Thermococcus kodakarensis
Synonyms
Synonyms
Commentary
Organism
ketopantoate reductase
-
Thermococcus kodakarensis
KPR
-
Thermococcus kodakarensis
Tk-KPR
-
Thermococcus kodakarensis
TK1968
-
Thermococcus kodakarensis
Temperature Optimum [°C]
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
70
-
assay at
Thermococcus kodakarensis
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
6.4
-
assay at
Thermococcus kodakarensis
Cofactor
Cofactor
Commentary
Organism
Structure
NADP+
the binding sites of CoA and NADP+ overlap, explaining the competitive manner of inhibition by CoA, binding structure analysis, overview
Thermococcus kodakarensis
Cloned(Commentary) (protein specific)
Commentary
Organism
gene TK1968, sequence comparisons, recombinant expression of wild-type and mutant enzymes in Escherichia coli strain Rosetta2 (DE3) pLysS
Thermococcus kodakarensis
Cofactor (protein specific)
Cofactor
Commentary
Organism
Structure
NADP+
the binding sites of CoA and NADP+ overlap, explaining the competitive manner of inhibition by CoA, binding structure analysis, overview
Thermococcus kodakarensis
Crystallization (Commentary) (protein specific)
Crystallization
Organism
purified enzyme in complex with CoA and 2-oxopantoate, hanging drop vapor diffusion method, mixing of 0.001 ml of 10 mg/ml protein and 1 mM CoA and 1 mM 2-oxopantoate with 0.001 ml of reservoir solution containing 100 mM Na acetate, pH 4.5, 20-25% v/v 2-methyl-2,4-pentanediol, and equilibration against 0.5 ml of reservoir solution, at 20°C, 3 days, X-ray diffraction structure determination and analysis at 1.65 A resolution, modeling by molecular replacement method using N-terminal (1-165 residues) and C-terminal (171-309 residues) domains of Ec-KPR structure, PDB ID 2OFP, as separated search models, respectively
Thermococcus kodakarensis
Engineering (protein specific)
Protein Variants
Commentary
Organism
C84A
site-directed mutagenesis, crystal structure analysis, overview
Thermococcus kodakarensis
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
CoA
feedback inhibition, competitive with NADPH, the binding sites of CoA and NADP+ overlap, explaining the competitive manner of inhibition by CoA, binding structure analysis, overview
Thermococcus kodakarensis
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
ID
(R)-pantoate + NADP+
Thermococcus kodakarensis
-
2-dehydropantoate + NADPH + H+
-
-
r
(R)-pantoate + NADP+
Thermococcus kodakarensis ATCC BAA-918
-
2-dehydropantoate + NADPH + H+
-
-
r
Purification (Commentary) (protein specific)
Commentary
Organism
recombinant wild-type and mutant enzymes from Escherichia coli strain Rosetta2 (DE3) pLysS by nickel affinity chromatography, avidin affinity chromatography, and dialysis
Thermococcus kodakarensis
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ID
(R)-pantoate + NADP+
-
741385
Thermococcus kodakarensis
2-dehydropantoate + NADPH + H+
-
-
-
r
(R)-pantoate + NADP+
substrate binding structure analysis, overview
741385
Thermococcus kodakarensis
2-dehydropantoate + NADPH + H+
-
-
-
r
(R)-pantoate + NADP+
-
741385
Thermococcus kodakarensis ATCC BAA-918
2-dehydropantoate + NADPH + H+
-
-
-
r
(R)-pantoate + NADP+
substrate binding structure analysis, overview
741385
Thermococcus kodakarensis ATCC BAA-918
2-dehydropantoate + NADPH + H+
-
-
-
r
Subunits (protein specific)
Subunits
Commentary
Organism
More
enzyme structure analysis and comparisons, overview
Thermococcus kodakarensis
Temperature Optimum [°C] (protein specific)
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
70
-
assay at
Thermococcus kodakarensis
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
6.4
-
assay at
Thermococcus kodakarensis
General Information
General Information
Commentary
Organism
additional information
CoA and 2-oxopantoate cooperatively trigger a conformational change from an open form to a closed enzyme form, structure analysis, overview
Thermococcus kodakarensis
physiological function
ketopantoate reductase (KPR) catalyzes the NAD(P)H-dependent reduction of 2-oxopantoate to pantoate, and is a target of the feedback inhibition by CoA in archaea. Coenzyme A (CoA) plays essential roles in a variety of metabolic pathways in all three domains of life. The biosynthesis pathway of CoA is strictly regulated by feedback inhibition. In bacteria and eukaryotes, pantothenate kinase is the target of feedback inhibition by CoA
Thermococcus kodakarensis
General Information (protein specific)
General Information
Commentary
Organism
additional information
CoA and 2-oxopantoate cooperatively trigger a conformational change from an open form to a closed enzyme form, structure analysis, overview
Thermococcus kodakarensis
physiological function
ketopantoate reductase (KPR) catalyzes the NAD(P)H-dependent reduction of 2-oxopantoate to pantoate, and is a target of the feedback inhibition by CoA in archaea. Coenzyme A (CoA) plays essential roles in a variety of metabolic pathways in all three domains of life. The biosynthesis pathway of CoA is strictly regulated by feedback inhibition. In bacteria and eukaryotes, pantothenate kinase is the target of feedback inhibition by CoA
Thermococcus kodakarensis
Other publictions for EC 1.1.1.169
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Synonyms
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
739822
Aikawa
Crystal structure of ketopanto ...
Thermococcus kodakarensis, Thermococcus kodakarensis ATCC BAA-918
Acta crystallogr. Sect. F
72
369-375
2016
-
-
1
1
3
-
1
-
-
-
-
2
-
9
-
-
1
-
-
-
-
-
2
1
4
1
-
-
-
1
-
-
1
-
-
-
-
-
1
1
1
3
-
-
1
-
-
-
-
-
2
-
-
-
1
-
-
-
-
2
1
1
-
-
-
1
-
-
-
-
1
1
-
-
-
741385
Aikawa
Crystal structure of archaeal ...
Thermococcus kodakarensis, Thermococcus kodakarensis ATCC BAA-918
Proteins
84
374-382
2016
-
-
1
1
1
-
1
-
-
-
-
2
-
13
-
-
1
-
-
-
-
-
4
1
4
1
-
-
-
1
-
-
1
-
-
-
-
-
1
1
1
1
-
-
1
-
-
-
-
-
2
-
-
-
1
-
-
-
-
4
1
1
-
-
-
1
-
-
-
-
2
2
-
-
-
740065
Sanchez
Evidence of kinetic cooperativ ...
Staphylococcus aureus
Biochemistry
54
3360-3369
2015
-
-
2
2
2
-
1
5
-
-
-
2
-
6
-
-
2
1
-
-
-
-
2
3
2
1
-
-
4
1
-
-
1
1
-
-
-
-
2
1
2
2
-
-
1
1
5
-
-
-
2
-
-
-
2
-
-
-
-
2
3
1
-
-
4
1
-
-
-
-
4
4
-
-
-
725293
Miller
PanG, a new ketopantoate reduc ...
Francisella tularensis subsp. novicida
J. Bacteriol.
195
965-976
2013
-
-
-
-
-
-
-
-
-
-
-
-
-
25
-
-
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-
-
-
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3
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-
-
-
-
-
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-
-
-
-
-
-
-
1
1
-
-
-
729136
Miyanaga
The crystal structure of D-man ...
Enterococcus faecalis, Enterococcus faecalis IAM10071
Biochem. Biophys. Res. Commun.
439
109-114
2013
-
-
-
-
-
-
-
-
-
-
-
2
-
4
-
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2
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2
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1
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1
-
-
-
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2
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-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
736827
Tomita
Identification and characteriz ...
Thermococcus kodakarensis, Thermococcus kodakarensis ATCC BAA-918
Mol. Microbiol.
90
307-321
2013
-
-
1
-
1
-
1
7
-
-
2
4
-
19
-
-
1
-
-
-
-
-
13
1
5
1
1
1
6
1
-
-
4
1
-
-
-
-
1
4
-
1
-
-
1
1
7
-
-
2
4
-
-
-
1
-
-
-
-
13
1
1
1
1
6
1
-
-
-
-
2
2
-
6
6
696603
Headey
Backbone assignments of the 34 ...
Escherichia coli
Biomol. NMR Assign.
2
93-96
2008
-
-
1
-
-
-
-
-
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1
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1
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1
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1
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2
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1
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1
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1
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1
-
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-
-
-
-
-
-
-
-
-
-
-
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684140
Ciulli
pH-tuneable binding of 2-phosp ...
Escherichia coli
Acta Crystallogr. Sect. D
63
171-178
2007
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1
-
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1
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4
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3
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3
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1
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1
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1
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3
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687675
Ciulli
Crystal structure of Escherich ...
Escherichia coli
J. Biol. Chem.
282
8487-8497
2007
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1
1
6
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3
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1
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4
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2
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2
1
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2
1
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2
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1
2
1
6
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3
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1
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-
2
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1
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2
1
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-
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-
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669806
Ciulli
Probing hot spots at protein-l ...
Escherichia coli
J. Med. Chem.
49
4992-5000
2006
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7
1
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1
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4
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1
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2
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2
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1
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3
6
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3
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7
6
1
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1
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2
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1
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667561
Ciulli
Biophysical tools to monitor e ...
Escherichia coli
Biochem. Soc. Trans.
33
767-771
2005
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1
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1
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1
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2
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667687
Lobley
The crystal structure of Esche ...
Escherichia coli
Biochemistry
44
8930-8939
2005
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1
1
7
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1
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1
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4
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1
1
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2
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1
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1
7
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1
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2
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654677
Zheng
Substrate specificity and kine ...
Escherichia coli
Biochemistry
42
11289-11296
2003
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1
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8
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1
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4
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7
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1
1
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1
1
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4
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1
4
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8
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1
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7
-
1
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-
-
1
1
-
-
-
-
-
-
-
-
656330
Merkamm
Ketopantoate reductase activit ...
Corynebacterium glutamicum
J. Biotechnol.
104
253-260
2003
-
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1
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1
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1
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9
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2
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2
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4
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1
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1
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2
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2
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286110
Matak-Vinkovic
Crystal structure of Escherich ...
Stenotrophomonas maltophilia, Salmonella enterica subsp. enterica serovar Typhimurium, Escherichia coli, Stenotrophomonas maltophilia 845
Biochemistry
40
14493-14500
2001
-
-
1
1
1
-
-
4
-
2
4
2
-
9
-
1
1
-
-
-
2
-
4
4
-
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-
2
-
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3
-
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-
-
1
3
1
1
-
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-
-
4
-
2
4
2
-
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1
1
-
-
2
-
4
4
-
-
-
2
-
-
-
-
-
-
-
-
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286108
Zheng
Kinetic and mechanistic analys ...
Escherichia coli
Biochemistry
39
3708-3717
2000
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1
-
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-
2
4
-
1
4
1
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4
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1
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1
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2
1
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2
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1
2
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2
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4
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1
4
1
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1
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1
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2
1
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-
-
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-
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-
-
-
-
-
-
286109
Zheng
Identification of active site ...
Escherichia coli
Biochemistry
39
16244-16251
2000
5
-
1
-
10
-
-
12
-
1
1
-
-
6
-
-
1
-
-
-
1
-
2
1
-
-
-
-
-
1
-
-
2
-
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5
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1
2
-
10
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12
-
1
1
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-
-
1
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1
-
2
1
-
-
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1
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Pantothenate production in Esc ...
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1
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1
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1
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1
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286107
Frodyma
ApbA, the ketopantoate reducta ...
Saccharomyces cerevisiae, Escherichia coli, Stenotrophomonas maltophilia, Salmonella enterica subsp. enterica serovar Typhimurium, Stenotrophomonas maltophilia 845, Escherichia coli BL21/lambdaDE3
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1
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2
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1
3
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15
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1
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6
-
12
2
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1
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1
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-
8
-
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1
8
-
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2
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1
3
-
-
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1
-
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6
-
12
2
1
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1
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-
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-
-
-
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286102
Kataoka
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Novel enzymic production of D- ...
Agrobacterium tumefaciens, Agrobacterium sp., Pseudomonas putida, Stenotrophomonas maltophilia
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4
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2
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3
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3
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4
-
2
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286103
Shimizu
Ketopantoic acid reductase of ...
Saccharomyces cerevisiae, Stenotrophomonas maltophilia, Stenotrophomonas maltophilia 845
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1988
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1
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10
4
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1
4
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10
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1
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2
1
6
1
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1
1
3
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2
-
2
4
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4
1
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-
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10
-
4
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1
4
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1
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-
2
1
6
1
1
1
3
-
2
-
2
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286105
Wilken
Ketopantoic acid and ketopanto ...
Saccharomyces cerevisiae, Escherichia coli
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2311-2314
1975
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-
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2
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2
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2
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2
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2
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2
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2
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King
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Separation and preliminary stu ...
Saccharomyces cerevisiae, Saccharomyces cerevisiae NRRL Y-2034
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2
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1
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2
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4
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2
1
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2
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2
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1
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2
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4
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2
1
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