Application | Comment | 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 (Comment) | Organism |
---|---|
expression of the expression construct pET28b-TEVpfDHODDELTA384413 in Escherichia coli strain BL21 | Plasmodium falciparum |
Crystallization (Comment) | 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 |
Protein Variants | Comment | 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 | Comment | 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 | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrial membrane | - |
Plasmodium berghei | 31966 | - |
mitochondrial membrane | - |
Plasmodium vivax | 31966 | - |
mitochondrial membrane | - |
Plasmodium falciparum | 31966 | - |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Plasmodium berghei | - |
- |
- |
Plasmodium falciparum | Q08210 | - |
- |
Plasmodium vivax | - |
- |
- |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged mutant DHODDELTA384-413 from Escherichia coli by affinity chromatography and gel filtration | Plasmodium falciparum |
Subunits | Comment | 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 | Comment | Organism |
---|---|---|
DHODH | - |
Plasmodium berghei |
DHODH | - |
Plasmodium vivax |
DHODH | - |
Plasmodium falciparum |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Plasmodium berghei |
8 | - |
assay at | Plasmodium vivax |
8 | - |
assay at | Plasmodium falciparum |
IC50 Value | IC50 Value Maximum | Comment | 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 |
General Information | Comment | 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 |