BRENDA - Enzyme Database
show all sequences of 1.3.5.2

Novel inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with anti-malarial activity in the mouse model

Booker, M.L.; Bastos, C.M.; Kramer, M.L.; Barker, R.H.; Skerlj, R.; Sidhu, A.B.; Deng, X.; Celatka, C.; Cortese, J.F.; Guerrero Bravo, J.E.; Crespo Llado, K.N.; Serrano, A.E.; Angulo-Barturen, I.; Jimenez-Diaz, M.B.; Viera, S.; Garuti, H.; Wittlin, S.; Papastogiannidis, P.; Lin, J.W.; Janse, C.J.; Khan, S.M.; J. Biol. Chem. 285, 33054-33064 (2010)

Data extracted from this reference:

Application
Application
Commentary
Organism
drug development
DHODH represents a potential target for anti-malarial therapy
Plasmodium berghei
drug development
DHODH represents a potential target for anti-malarial therapy
Plasmodium vivax
drug development
DHODH represents a potential target for anti-malarial therapy
Plasmodium falciparum
medicine
DHODH represents a potential target for anti-malarial therapy
Plasmodium berghei
medicine
DHODH represents a potential target for anti-malarial therapy
Plasmodium vivax
medicine
DHODH represents a potential target for anti-malarial therapy
Plasmodium falciparum
Cloned(Commentary)
Cloned (Commentary)
Organism
expression of the expression construct pET28b-TEVpfDHODDELTA384–413 in Escherichia coli strain BL21
Plasmodium falciparum
Crystallization (Commentary)
Crystallization (Commentary)
Organism
purified recombinant His-tagged mutant DHODDELTA384-413 free or in complex with Genz-667348, hanging drop vapour diffusion method, 20°C, mixing reservoir solution A containing 0.16 M ammonium sulfate, 0.1 M sodium acetate, pH 4.4, 14-15% PEG 4000, 25% glycerol, and 10 mM DTT, with an equal volume of 20 mg/ml protein pre-equilibrated with 0.6 mM Genz-667348, and 2 mM dihydroorotate, X-ray diffraction structure determination and analysis at 2.4 A resolution, molecular replacement
Plasmodium falciparum
Engineering
Protein Variants
Commentary
Organism
additional information
deletion of a surface loop in PfDHODH containing amino acid residues 384-413, which facilitates crystallization of the enzyme with the triazolopyrimidine class of inhibitors. An N-terminal deletion that removes the mitochondrial membrane-spanning domain as well as residues that are N-terminal to this region does not lead to better crystal yields. Replacement of the thrombin site and T7 tag sequence in the vector with the TEV protease site
Plasmodium falciparum
Inhibitors
Inhibitors
Commentary
Organism
Structure
Genz-667348
-
Plasmodium berghei
Genz-667348
-
Plasmodium falciparum
Genz-667348
-
Plasmodium vivax
Genz-668857
-
Plasmodium berghei
Genz-668857
-
Plasmodium falciparum
Genz-668857
-
Plasmodium vivax
Genz-669178
-
Plasmodium berghei
Genz-669178
-
Plasmodium falciparum
Genz-669178
-
Plasmodium vivax
additional information
drug screening and identification of a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolar in vitro potency against DHODH, selective for the parasite enzymes over human DHODH, tolerability in the mouse, overview
Plasmodium berghei
additional information
drug screening and identifictaion of a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolarin vitro potency against DHODH, selective for the parasite enzymes over human DHODH, tolerability in the mouse, overview
Plasmodium falciparum
additional information
drug screening and identification of a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolar in vitro potency against DHODH, selective for the parasite enzymes over human DHODH, tolerability in the mouse, overview
Plasmodium vivax
Localization
Localization
Commentary
Organism
GeneOntology No.
Textmining
mitochondrial membrane
-
Plasmodium berghei
31966
-
mitochondrial membrane
-
Plasmodium vivax
31966
-
mitochondrial membrane
-
Plasmodium falciparum
31966
-
Organism
Organism
UniProt
Commentary
Textmining
Plasmodium berghei
-
-
-
Plasmodium falciparum
Q08210
-
-
Plasmodium vivax
-
-
-
Purification (Commentary)
Purification (Commentary)
Organism
recombinant His-tagged mutant DHODDELTA384-413 from Escherichia coli by affinity chromatography and gel filtration
Plasmodium falciparum
Subunits
Subunits
Commentary
Organism
More
Plasmodium enzyme structure comparisons, molecular modeling, overview
Plasmodium berghei
More
Plasmodium enzyme structure comparisons, molecular modeling, overview
Plasmodium vivax
More
Plasmodium enzyme structure comparisons, molecular modeling, overview
Plasmodium falciparum
Synonyms
Synonyms
Commentary
Organism
DHODH
-
Plasmodium berghei
DHODH
-
Plasmodium vivax
DHODH
-
Plasmodium falciparum
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
8
-
assay at
Plasmodium berghei
8
-
assay at
Plasmodium vivax
8
-
assay at
Plasmodium falciparum
IC50 Value
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
0.000012
-
pH 8.0, temperature not specified in the publication
Plasmodium berghei
Genz-668857
0.000014
-
pH 8.0, temperature not specified in the publication
Plasmodium berghei
Genz-667348
0.000015
-
pH 8.0, temperature not specified in the publication
Plasmodium vivax
Genz-668857
0.000015
-
pH 8.0, temperature not specified in the publication
Plasmodium vivax
Genz-669178
0.000022
-
pH 8.0, temperature not specified in the publication
Plasmodium falciparum
Genz-667348
0.00004
-
pH 8.0, temperature not specified in the publication
Plasmodium berghei
Genz-669178
0.000042
-
pH 8.0, temperature not specified in the publication
Plasmodium vivax
Genz-667348
0.000044
-
pH 8.0, temperature not specified in the publication
Plasmodium falciparum
Genz-668857
0.00005
-
pH 8.0, temperature not specified in the publication
Plasmodium falciparum
Genz-669178
Application (protein specific)
Application
Commentary
Organism
drug development
DHODH represents a potential target for anti-malarial therapy
Plasmodium berghei
drug development
DHODH represents a potential target for anti-malarial therapy
Plasmodium vivax
drug development
DHODH represents a potential target for anti-malarial therapy
Plasmodium falciparum
medicine
DHODH represents a potential target for anti-malarial therapy
Plasmodium berghei
medicine
DHODH represents a potential target for anti-malarial therapy
Plasmodium vivax
medicine
DHODH represents a potential target for anti-malarial therapy
Plasmodium falciparum
Cloned(Commentary) (protein specific)
Commentary
Organism
expression of the expression construct pET28b-TEVpfDHODDELTA384–413 in Escherichia coli strain BL21
Plasmodium falciparum
Crystallization (Commentary) (protein specific)
Crystallization
Organism
purified recombinant His-tagged mutant DHODDELTA384-413 free or in complex with Genz-667348, hanging drop vapour diffusion method, 20°C, mixing reservoir solution A containing 0.16 M ammonium sulfate, 0.1 M sodium acetate, pH 4.4, 14-15% PEG 4000, 25% glycerol, and 10 mM DTT, with an equal volume of 20 mg/ml protein pre-equilibrated with 0.6 mM Genz-667348, and 2 mM dihydroorotate, X-ray diffraction structure determination and analysis at 2.4 A resolution, molecular replacement
Plasmodium falciparum
Engineering (protein specific)
Protein Variants
Commentary
Organism
additional information
deletion of a surface loop in PfDHODH containing amino acid residues 384-413, which facilitates crystallization of the enzyme with the triazolopyrimidine class of inhibitors. An N-terminal deletion that removes the mitochondrial membrane-spanning domain as well as residues that are N-terminal to this region does not lead to better crystal yields. Replacement of the thrombin site and T7 tag sequence in the vector with the TEV protease site
Plasmodium falciparum
IC50 Value (protein specific)
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
0.000012
-
pH 8.0, temperature not specified in the publication
Plasmodium berghei
Genz-668857
0.000014
-
pH 8.0, temperature not specified in the publication
Plasmodium berghei
Genz-667348
0.000015
-
pH 8.0, temperature not specified in the publication
Plasmodium vivax
Genz-668857
0.000015
-
pH 8.0, temperature not specified in the publication
Plasmodium vivax
Genz-669178
0.000022
-
pH 8.0, temperature not specified in the publication
Plasmodium falciparum
Genz-667348
0.00004
-
pH 8.0, temperature not specified in the publication
Plasmodium berghei
Genz-669178
0.000042
-
pH 8.0, temperature not specified in the publication
Plasmodium vivax
Genz-667348
0.000044
-
pH 8.0, temperature not specified in the publication
Plasmodium falciparum
Genz-668857
0.00005
-
pH 8.0, temperature not specified in the publication
Plasmodium falciparum
Genz-669178
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
Genz-667348
-
Plasmodium berghei
Genz-667348
-
Plasmodium vivax
Genz-667348
-
Plasmodium falciparum
Genz-668857
-
Plasmodium berghei
Genz-668857
-
Plasmodium vivax
Genz-668857
-
Plasmodium falciparum
Genz-669178
-
Plasmodium berghei
Genz-669178
-
Plasmodium vivax
Genz-669178
-
Plasmodium falciparum
additional information
drug screening and identification of a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolar in vitro potency against DHODH, selective for the parasite enzymes over human DHODH, tolerability in the mouse, overview
Plasmodium berghei
additional information
drug screening and identification of a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolar in vitro potency against DHODH, selective for the parasite enzymes over human DHODH, tolerability in the mouse, overview
Plasmodium vivax
additional information
drug screening and identifictaion of a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolarin vitro potency against DHODH, selective for the parasite enzymes over human DHODH, tolerability in the mouse, overview
Plasmodium falciparum
Localization (protein specific)
Localization
Commentary
Organism
GeneOntology No.
Textmining
mitochondrial membrane
-
Plasmodium berghei
31966
-
mitochondrial membrane
-
Plasmodium vivax
31966
-
mitochondrial membrane
-
Plasmodium falciparum
31966
-
Purification (Commentary) (protein specific)
Commentary
Organism
recombinant His-tagged mutant DHODDELTA384-413 from Escherichia coli by affinity chromatography and gel filtration
Plasmodium falciparum
Subunits (protein specific)
Subunits
Commentary
Organism
More
Plasmodium enzyme structure comparisons, molecular modeling, overview
Plasmodium berghei
More
Plasmodium enzyme structure comparisons, molecular modeling, overview
Plasmodium vivax
More
Plasmodium enzyme structure comparisons, molecular modeling, overview
Plasmodium falciparum
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
8
-
assay at
Plasmodium berghei
8
-
assay at
Plasmodium vivax
8
-
assay at
Plasmodium falciparum
General Information
General Information
Commentary
Organism
physiological function
DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway
Plasmodium berghei
physiological function
DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway
Plasmodium vivax
physiological function
DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway
Plasmodium falciparum
General Information (protein specific)
General Information
Commentary
Organism
physiological function
DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway
Plasmodium berghei
physiological function
DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway
Plasmodium vivax
physiological function
DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway
Plasmodium falciparum
Other publictions for EC 1.3.5.2
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)
740844
Zhu
Design, synthesis, X-ray cryst ...
Homo sapiens
J. Med. Chem.
58
1123-1139
2015
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-
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56
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1
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6
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2
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1
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1
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54
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1
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54
56
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2
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-
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-
740847
Munier-Lehmann
Original 2-(3-alkoxy-1H-pyrazo ...
Homo sapiens
J. Med. Chem.
58
860-877
2015
-
-
1
-
-
-
46
-
-
-
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6
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1
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2
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1
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1
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46
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1
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2
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-
-
-
-
-
-
-
-
-
-
740478
Hey-Mogensen
Production of superoxide/H2O2 ...
Rattus norvegicus
Free Radic. Biol. Med.
72
149-155
2014
-
-
-
-
-
-
2
-
3
-
-
-
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7
-
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3
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1
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1
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2
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3
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3
-
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1
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-
-
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-
-
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741097
Stocks
Novel inhibitors of the Plasmo ...
Plasmodium falciparum
Parasitology
141
50-65
2014
-
-
-
-
-
-
12
-
1
-
-
1
-
5
-
-
-
-
-
-
-
-
1
-
2
-
-
-
-
-
-
-
1
-
-
2
-
-
-
1
-
-
-
2
12
-
-
1
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
725920
Hegewald
Identification of dihydroorota ...
Toxoplasma gondii
Mol. Biochem. Parasitol.
190
6-15
2013
-
-
1
-
2
-
4
8
1
-
1
-
-
10
-
-
1
-
-
-
-
-
3
1
1
-
-
-
6
-
-
-
1
4
-
4
-
-
1
1
-
2
-
4
5
4
8
1
-
1
-
-
-
-
1
-
-
-
-
3
1
-
-
-
6
-
-
-
-
-
-
-
-
8
8
725670
Bedingfield
Factors influencing the specif ...
Plasmodium falciparum, Homo sapiens
J. Med. Chem.
55
5841-5850
2012
-
-
-
1
-
-
8
-
-
-
-
-
-
6
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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-
-
-
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-
-
8
-
-
-
-
1
-
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8
8
-
-
-
-
-
-
-
-
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-
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-
-
-
-
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-
-
-
-
-
-
-
-
-
-
-
-
-
-
725919
Hortua Triana
Biochemical and molecular char ...
Toxoplasma gondii
Mol. Biochem. Parasitol.
184
71-81
2012
-
-
-
-
-
-
4
7
1
-
-
-
-
12
-
-
-
-
-
-
1
-
7
-
-
-
-
-
7
-
-
-
-
-
-
3
-
-
-
-
-
-
-
3
4
-
7
1
-
-
-
-
-
-
-
-
-
1
-
7
-
-
-
-
7
-
-
-
-
-
1
1
-
-
-
724182
Couto
Site directed spin labeling st ...
Escherichia coli
Biochem. Biophys. Res. Commun.
414
487-492
2011
-
-
-
-
4
-
-
-
1
-
-
-
-
5
-
-
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-
-
-
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1
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4
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1
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-
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-
-
-
-
-
-
-
-
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-
-
-
-
-
-
711913
Ojha
Chemometric modeling, docking ...
Plasmodium falciparum
Eur. J. Med. Chem.
45
4645-4656
2010
-
-
-
-
-
-
30
-
1
-
-
1
-
1
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
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1
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-
-
-
-
-
1
-
-
-
-
30
-
-
1
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
712071
Hail
Dihydroorotate dehydrogenase i ...
Homo sapiens
Free Radic. Biol. Med.
49
109-116
2010
-
-
1
-
-
-
1
-
1
-
-
1
-
4
-
-
-
-
-
7
-
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1
-
1
-
-
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1
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-
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1
1
-
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-
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1
-
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1
-
-
1
-
-
-
-
-
7
-
-
1
-
-
-
-
-
-
-
-
-
1
1
1
1
-
-
712147
Phillips
Plasmodium dihydroorotate dehy ...
Homo sapiens, Plasmodium falciparum
Infect. Disord. Drug Targets
10
226-239
2010
1
-
-
-
-
-
62
-
2
-
-
2
-
13
-
-
-
-
-
-
-
-
4
-
2
-
-
-
-
-
-
-
3
-
-
50
1
-
-
3
-
-
-
50
62
-
-
2
-
-
2
-
-
-
-
-
-
-
-
4
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
712475
Booker
Novel inhibitors of Plasmodium ...
Plasmodium berghei, Plasmodium vivax, Plasmodium falciparum
J. Biol. Chem.
285
33054-33064
2010
-
6
1
1
1
-
12
-
3
-
-
-
-
15
-
-
1
-
-
-
-
-
-
3
3
-
-
-
-
3
-
-
-
-
-
9
-
6
1
-
1
1
-
9
12
-
-
3
-
-
-
-
-
-
1
-
-
-
-
-
3
-
-
-
-
3
-
-
-
-
3
3
-
-
-
713150
Schaefer
Region-specific distribution o ...
Rattus norvegicus
Nucleosides Nucleotides Nucleic Acids
29
476-481
2010
-
-
-
-
-
-
-
-
1
-
-
-
-
7
-
-
-
-
-
16
-
-
-
-
1
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-
-
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-
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-
-
-
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-
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1
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-
-
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-
-
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16
-
-
-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
696348
Fagan
Roles in binding and chemistry ...
Escherichia coli
Biochemistry
48
7169-7178
2009
-
-
-
-
6
-
-
-
-
-
-
-
-
6
-
-
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1
-
-
-
-
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6
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-
-
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-
-
-
696365
Kow
Disruption of the proton relay ...
Escherichia coli
Biochemistry
48
9801-9809
2009
-
-
-
-
5
-
-
-
-
-
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-
-
4
-
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1
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5
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-
-
-
-
-
-
-
-
-
-
-
-
698938
Deng
Structural plasticity of malar ...
Plasmodium falciparum
J. Biol. Chem.
284
26999-27009
2009
-
-
-
1
4
-
3
-
-
-
-
-
-
4
-
-
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1
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3
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1
-
-
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-
-
-
-
-
-
-
-
-
-
-
-
699460
Davies
Structure-based design, synthe ...
Homo sapiens, Plasmodium falciparum
J. Med. Chem.
52
2683-2693
2009
-
-
-
2
-
-
18
-
-
-
-
-
-
7
-
-
-
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18
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700138
Baumann
Dihydroorotate dehydrogenase i ...
Homo sapiens
Mol. Cancer Ther.
8
366-375
2009
-
1
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-
-
1
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2
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1
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-
712682
Gujjar
Identification of a metabolica ...
Plasmodium falciparum
J. Med. Chem.
52
1864-1872
2009
-
-
-
-
-
-
41
-
1
-
-
-
-
8
-
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1
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1
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41
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1
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-
1
-
-
-
-
-
-
-
-
-
696249
Malmquist
Analysis of flavin oxidation a ...
Plasmodium falciparum
Biochemistry
47
2466-2475
2008
-
-
1
-
9
-
1
20
1
-
-
-
-
10
-
-
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-
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3
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30
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6
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1
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9
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6
1
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20
1
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3
-
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30
-
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-
-
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-
-
-
-
-
696289
Walse
The structures of human dihydr ...
Homo sapiens
Biochemistry
47
8929-8936
2008
-
-
1
1
-
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2
-
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-
-
-
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6
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1
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2
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1
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1
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2
2
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1
-
-
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-
-
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-
-
-
-
-
-
-
-
-
697767
Deguchi
Suppression of immunoglobulin ...
Homo sapiens, Mus musculus
Eur. J. Pharmacol.
601
163-170
2008
-
-
-
-
-
-
4
-
-
-
-
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-
10
-
-
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4
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4
4
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-
-
-
-
-
-
-
-
698855
Patel
Identification and characteriz ...
Plasmodium berghei, Plasmodium vivax, Plasmodium falciparum
J. Biol. Chem.
283
35078-35085
2008
-
-
-
-
-
-
12
-
-
-
-
-
-
8
-
-
-
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12
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12
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-
-
-
-
-
-
-
-
-
-
-
675315
Heikkilä
Design and synthesis of potent ...
Homo sapiens, Plasmodium falciparum
J. Med. Chem.
50
186-191
2007
-
3
2
-
6
-
13
12
-
-
-
-
-
7
-
-
2
-
-
-
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4
-
4
-
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8
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2
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2
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3
2
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6
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2
13
2
12
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2
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-
-
4
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-
8
-
-
-
-
-
-
-
-
-
-
684555
Zameitat
Functional expression of human ...
Homo sapiens
Appl. Environ. Microbiol.
73
3371-3379
2007
-
-
1
-
-
-
1
-
-
-
-
-
-
15
-
-
-
-
-
-
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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-
-
-
-
-
-
-
-
-
-
-
-
-
-
672109
Fagan
Mechanism of flavin reduction ...
Escherichia coli, Homo sapiens
Biochemistry
45
14926-14932
2006
-
2
2
-
-
-
-
-
-
-
-
-
-
4
-
-
2
-
-
-
-
-
2
-
4
-
-
-
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2
-
2
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2
2
2
-
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-
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-
-
-
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2
-
-
-
-
2
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
673547
Zameitat
Biochemical characterization o ...
Candida albicans
FEBS J.
273
3183-3191
2006
1
1
1
-
2
-
2
6
-
-
1
-
-
15
-
-
1
-
-
-
1
-
7
1
1
-
-
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2
1
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1
-
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1
1
1
1
-
2
-
-
2
-
6
-
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1
-
-
-
-
1
-
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1
-
7
1
-
-
-
2
1
-
-
-
-
-
-
-
-
-
675294
Baumgartner
Dual binding mode of a novel s ...
Homo sapiens
J. Med. Chem.
49
1239-1247
2006
-
1
-
1
-
-
1
-
-
-
-
-
-
4
-
-
1
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
-
-
-
-
1
-
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1
-
-
-
1
-
-
-
-
-
-
-
-
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1
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
675614
Small
Hydrogen bonding pathways in h ...
Homo sapiens
J. Phys. Chem. B
110
19704-19710
2006
-
1
-
-
1
-
-
-
-
-
-
-
-
6
-
-
-
-
-
-
-
-
2
-
1
-
-
-
-
-
-
-
2
-
-
-
-
1
-
2
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
656285
Baldwin
High-throughput screening for ...
Plasmodium falciparum
J. Biol. Chem.
280
21847-21853
2005
-
-
-
-
2
-
13
6
-
-
-
-
-
4
-
-
-
-
-
-
-
-
2
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
13
-
6
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
654974
Leban
Discovery of a novel series of ...
Homo sapiens
Bioorg. Med. Chem. Lett.
14
55-58
2004
-
-
-
-
-
-
31
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
31
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
655794
Shi
Multiple states of the Tyr318L ...
Escherichia coli
J. Am. Chem. Soc.
126
6914-6922
2004
-
-
-
-
1
-
-
-
1
-
-
-
-
3
-
-
-
-
-
-
-
-
2
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
657301
Hansen
Inhibitor binding in a class 2 ...
Rattus norvegicus
Protein Sci.
13
1031-1042
2004
-
-
-
1
1
-
2
-
-
-
-
-
-
8
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
655559
Ullrich
Plant dihydroorotate dehydroge ...
Arabidopsis thaliana
FEBS Lett.
529
346-350
2002
-
-
-
-
1
-
-
4
-
-
1
-
-
9
-
-
-
1
-
-
-
-
6
1
-
-
-
-
2
1
-
-
1
-
-
-
-
-
-
1
-
1
-
-
-
-
4
-
-
1
-
-
-
-
-
-
-
-
-
6
1
-
-
-
2
1
-
-
-
-
-
-
-
-
-
655723
Loffler
Drosophila melanogaster dihydr ...
Drosophila melanogaster
Insect Biochem. Mol. Biol.
32
1159-1169
2002
-
-
-
-
3
-
4
8
-
-
-
-
-
12
-
-
1
-
-
-
1
-
8
-
-
-
-
-
4
1
-
-
-
-
-
-
-
-
-
-
-
3
-
-
4
-
8
-
-
-
-
-
-
-
1
-
-
1
-
8
-
-
-
-
4
1
-
-
-
-
-
-
-
-
-
656088
Baldwin
Malarial dihydroorotate dehydr ...
Homo sapiens, Plasmodium falciparum
J. Biol. Chem.
277
41827-41834
2002
-
-
1
-
2
-
10
8
1
-
-
-
-
4
-
-
-
-
-
-
-
-
5
-
-
-
-
-
8
1
-
-
6
5
-
-
-
-
1
6
-
2
-
-
10
5
8
1
-
-
-
-
-
-
-
-
-
-
-
5
-
-
-
-
8
1
-
-
-
-
-
-
-
-
-
656747
Takashima
Characterization of the dihydr ...
Trypanosoma cruzi
Mol. Biochem. Parasitol.
122
189-200
2002
-
-
-
-
-
-
-
-
1
-
2
-
-
8
-
-
1
-
-
-
3
-
2
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
1
-
2
-
-
-
-
1
-
-
3
-
2
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
390919
Palfey
Insight into the chemistry of ...
Escherichia coli
Biochemistry
40
4381-4390
2001
-
-
-
-
1
-
-
-
1
-
-
1
-
4
-
-
-
1
-
-
-
-
4
1
1
-
-
-
1
-
-
1
1
-
-
-
-
-
-
1
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
4
1
-
-
-
1
-
-
1
-
-
-
-
-
-
-
390924
Ullrich
Recombinant expression of N-te ...
Homo sapiens, Mus musculus, Rattus norvegicus
Eur. J. Biochem.
268
1861-1868
2001
-
3
3
-
-
-
15
6
7
-
1
3
-
14
-
-
3
-
-
-
3
3
6
2
3
-
-
-
3
5
-
-
3
-
-
-
-
3
3
3
-
-
-
-
15
-
6
7
-
1
3
-
-
-
3
-
-
3
3
6
2
-
-
-
3
5
-
-
-
-
-
-
-
-
-
391246
McLean
Multiple inhibitor analysis of ...
Homo sapiens
Biochemistry
40
2194-2200
2001
-
-
-
-
-
-
2
-
-
-
-
-
-
4
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
390914
Rowland
Crystallization and preliminar ...
Escherichia coli
Acta Crystallogr. Sect. D
56
659-661
2000
-
-
-
2
-
-
-
-
1
-
-
1
-
6
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
2
-
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
390920
Liu
Structures of human dihydrooro ...
Homo sapiens
Structure
8
25-33
2000
-
-
-
1
-
-
2
-
-
-
-
-
-
3
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
1
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
390930
Marcinkeviciene
A second dihydroorotate dehydr ...
Enterococcus faecalis
Arch. Biochem. Biophys.
377
178-186
2000
-
1
2
-
-
-
3
1
-
-
2
1
-
10
-
-
1
1
-
-
-
1
5
1
-
1
-
-
-
1
-
-
2
2
-
-
-
1
2
2
-
-
-
-
3
2
1
-
-
2
1
-
-
-
1
-
-
-
1
5
1
1
-
-
-
1
-
-
-
-
-
-
-
-
-
391242
Knecht
Kinetics of inhibition of huma ...
Homo sapiens, Rattus norvegicus
Chem. Biol. Interact.
124
61-76
2000
-
-
-
-
-
-
10
-
-
-
-
-
-
16
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
8
-
-
-
-
-
-
-
-
-
-
10
8
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
390918
Bjoernberg
The activity of Escherichia co ...
Escherichia coli, Lactococcus lactis
Biochemistry
38
2899-2908
1999
-
-
1
-
6
-
1
6
2
-
6
2
-
7
1
-
1
3
-
-
12
1
7
4
2
4
-
3
-
1
-
-
2
1
-
-
-
-
1
2
-
6
-
-
1
1
6
2
-
6
2
-
1
-
1
-
-
12
1
7
4
4
-
3
-
1
-
-
-
-
-
-
-
-
-
390923
Bruneau
-
Purification of human dihydro- ...
Homo sapiens
Biochem. J.
336
299-303
1998
-
2
-
-
-
-
5
-
1
-
3
-
-
2
-
-
2
-
-
2
-
1
-
2
1
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
5
-
-
1
-
3
-
-
-
-
2
-
2
-
1
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
390926
Bader
Expression, purification, and ...
Homo sapiens, Rattus norvegicus
Protein Expr. Purif.
13
414-422
1998
-
2
3
-
-
-
6
8
2
-
2
2
-
24
-
-
2
-
-
-
5
-
8
2
-
-
-
-
-
6
-
-
3
-
-
-
-
2
3
3
-
-
-
-
7
-
8
2
-
2
2
-
-
-
2
-
-
5
-
8
2
-
-
-
-
6
-
-
-
-
-
-
-
-
-
390921
Davis
Histidine to alanine mutants o ...
Homo sapiens
Biochem. Pharmacol.
54
459-465
1997
-
1
1
-
10
-
3
3
1
-
1
-
-
5
-
-
-
-
-
1
-
-
2
-
1
1
-
-
1
-
-
-
-
-
-
-
-
1
1
-
-
10
-
-
3
-
3
1
-
1
-
-
-
-
-
-
1
-
-
2
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
391235
Knecht
Rat dihydroorotate dehydrogena ...
Rattus norvegicus
Protein Expr. Purif.
10
89-99
1997
-
-
1
-
-
-
-
2
2
-
-
-
-
15
-
-
-
-
-
1
-
-
2
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
1
-
-
-
-
-
-
2
2
-
-
-
-
-
-
-
-
1
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
390925
Loeffler
Catalytic enzyme histochemistr ...
Bos taurus, Cavia porcellus, Homo sapiens, Mus musculus, Sus scrofa, Rattus norvegicus
Histochem. Cell Biol.
105
119-128
1996
-
-
-
-
-
-
17
-
6
-
-
6
-
21
-
-
-
6
-
24
8
6
8
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
17
-
-
6
-
-
6
-
-
-
-
-
24
8
6
8
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
391233
Knecht
Functional expression of a fra ...
Homo sapiens
Eur. J. Biochem.
240
292-301
1996
-
-
-
-
-
-
1
4
2
-
1
-
-
6
-
-
-
-
-
-
-
-
3
1
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
1
2
4
2
-
1
-
-
-
-
-
-
-
-
-
3
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
391241
Davis
The immunosuppressive metaboli ...
Homo sapiens
Biochemistry
35
1270-1273
1996
-
-
-
-
-
-
1
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
390922
Copeland
Recombinant human dihydroorota ...
Homo sapiens
Arch. Biochem. Biophys.
323
79-86
1995
-
1
2
-
-
-
2
1
2
-
4
1
-
8
-
-
1
-
-
1
1
1
2
2
2
-
-
-
-
2
-
-
1
2
-
-
-
1
2
1
-
-
-
-
3
2
1
2
-
4
1
-
-
-
1
-
1
1
1
2
2
-
-
-
-
2
-
-
-
-
-
-
-
-
-
390929
Krungkrai
Purification, characterization ...
Plasmodium falciparum
Biochim. Biophys. Acta
1243
351-360
1995
-
-
-
-
-
-
13
4
6
-
2
1
-
11
-
-
2
-
-
4
1
2
4
2
-
-
-
-
2
1
-
-
-
7
-
-
-
-
-
-
-
-
-
-
15
7
4
6
-
2
1
-
-
-
2
-
4
1
2
4
2
-
-
-
2
1
-
-
-
-
-
-
-
-
-
391226
Hines
Analysis of the kinetic mechan ...
Bos taurus
Biochemistry
28
1222-1226
1989
-
-
-
-
-
-
2
7
3
1
-
-
-
4
-
-
-
1
-
3
-
-
6
-
-
-
-
-
4
-
-
-
1
2
-
-
-
-
-
1
-
-
-
-
2
2
7
3
1
-
-
-
-
-
-
-
3
-
-
6
-
-
-
-
4
-
-
-
-
-
-
-
-
-
-
391224
Hines
Purification and properties of ...
Bos taurus
J. Biol. Chem.
261
11386-11392
1986
-
-
-
-
-
-
5
5
3
-
1
-
-
5
-
-
1
-
-
3
1
1
14
1
-
-
-
2
-
1
1
2
-
-
-
-
-
-
-
-
-
-
-
-
5
-
5
3
-
1
-
-
-
-
1
-
3
1
1
14
1
-
-
2
-
1
1
2
-
-
-
-
-
-
-
391229
Miersch
-
Properties and subcellular loc ...
Solanum lycopersicum
J. Plant Physiol.
122
55-66
1986
-
-
-
-
-
1
-
-
1
-
-
-
-
1
-
-
1
-
-
1
-
1
1
-
-
1
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
1
-
-
-
-
-
-
1
-
1
-
1
1
-
1
-
-
-
2
-
-
-
-
-
-
-
-
-
391221
Forman
Mammalian dihydroorotate dehyd ...
Rattus norvegicus
Arch. Biochem. Biophys.
191
23-31
1978
-
-
-
-
-
-
3
1
1
2
-
1
-
1
-
-
-
-
-
1
-
-
6
-
-
-
-
-
-
1
-
-
2
-
-
-
-
-
-
2
-
-
-
-
3
-
1
1
2
-
1
-
-
-
-
-
1
-
-
6
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
391223
Miller
Dihydroorotate dehydrogenase ( ...
Neurospora crassa
Methods Enzymol.
51
63-69
1978
-
-
-
-
-
1
2
-
1
1
1
1
-
1
-
1
1
2
-
1
1
1
5
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
1
-
2
-
-
1
1
1
1
-
-
1
1
-
1
1
1
5
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
391227
Karibian
Dihydroorotate dehydrogenase ( ...
Escherichia coli
Methods Enzymol.
51
58-63
1978
-
-
-
-
-
-
4
1
-
-
1
1
-
1
-
-
1
-
-
-
1
1
4
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
4
-
1
-
-
1
1
-
-
-
1
-
-
1
1
4
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-