Cloned (Comment) | Organism |
---|---|
expressed in Escherichia coli Rosetta 2(DE3) pLysS cells | Plasmodium berghei |
expressed in Escherichia coli Rosetta 2(DE3) pLysS cells | Plasmodium chabaudi |
expressed in Escherichia coli Rosetta 2(DE3) pLysS cells | Plasmodium vivax |
expressed in Escherichia coli Rosetta 2(DE3) pLysS cells | Plasmodium falciparum |
Crystallization (Comment) | Organism |
---|---|
enzyme in complex with inhibitor ML1, hanging drop vapor diffusion method, using 10% (w/v) PEG 5000 MME, 5% (w/v) tacsimate, 0.1M HEPES pH 7.0, 1 5mM spermidine, and 25% (v/v) glycerol. Enzyme in complex with inhibitor ML10, hanging drop vapor diffusion method, using 15.5% (w/v) PEG 3350, 0.1M HEPES pH 7, 0.1 M succinate pH 7.0 | Plasmodium vivax |
Protein Variants | Comment | Organism |
---|---|---|
T618Q | the mutant exhibits a reduced sensitivity to many inhibitors of between 500 and more than 100000fold as compared to the wild type enzyme | Plasmodium falciparum |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
4-[2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium berghei | |
4-[2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium chabaudi | |
4-[2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium falciparum | |
4-[2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium vivax | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium berghei | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium chabaudi | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium falciparum | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium vivax | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium berghei | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium chabaudi | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium falciparum | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | - |
Plasmodium vivax | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-yl]pyrimidin-2-amine | - |
Plasmodium berghei | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-yl]pyrimidin-2-amine | - |
Plasmodium chabaudi | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-yl]pyrimidin-2-amine | - |
Plasmodium falciparum | |
4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-yl]pyrimidin-2-amine | - |
Plasmodium vivax | |
4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | - |
Plasmodium berghei | |
4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | - |
Plasmodium chabaudi | |
4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | - |
Plasmodium falciparum | |
4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | - |
Plasmodium vivax | |
N-(3-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]phenyl)methanesulfonamide | - |
Plasmodium berghei | |
N-(3-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]phenyl)methanesulfonamide | - |
Plasmodium chabaudi | |
N-(3-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]phenyl)methanesulfonamide | - |
Plasmodium falciparum | |
N-(3-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]phenyl)methanesulfonamide | - |
Plasmodium vivax | |
N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | - |
Plasmodium berghei | |
N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | - |
Plasmodium chabaudi | |
N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | - |
Plasmodium falciparum | |
N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | - |
Plasmodium vivax | |
N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | - |
Plasmodium berghei | |
N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | - |
Plasmodium chabaudi | |
N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | - |
Plasmodium falciparum | |
N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | - |
Plasmodium vivax | |
N-(cyclopropylmethyl)-4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | - |
Plasmodium berghei | |
N-(cyclopropylmethyl)-4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | - |
Plasmodium chabaudi | |
N-(cyclopropylmethyl)-4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | - |
Plasmodium falciparum | |
N-(cyclopropylmethyl)-4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | - |
Plasmodium vivax | |
N-[5-(3-[2-[(cyclopropylmethyl)amino]pyrimidin-4-yl]-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl)-2-fluorophenyl]methanesulfonamide | most potent inhibitor | Plasmodium berghei | |
N-[5-(3-[2-[(cyclopropylmethyl)amino]pyrimidin-4-yl]-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl)-2-fluorophenyl]methanesulfonamide | most potent inhibitor | Plasmodium chabaudi | |
N-[5-(3-[2-[(cyclopropylmethyl)amino]pyrimidin-4-yl]-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl)-2-fluorophenyl]methanesulfonamide | most potent inhibitor | Plasmodium falciparum | |
N-[5-(3-[2-[(cyclopropylmethyl)amino]pyrimidin-4-yl]-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl)-2-fluorophenyl]methanesulfonamide | most potent inhibitor | Plasmodium vivax |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Plasmodium berghei | - |
- |
- |
Plasmodium chabaudi | - |
- |
- |
Plasmodium falciparum | Q8I719 | - |
- |
Plasmodium vivax | A5K0N4 | - |
- |
Plasmodium vivax Salvador | A5K0N4 | - |
- |
Purification (Comment) | Organism |
---|---|
HiTrap TALON (cobalt) column chromatography | Plasmodium berghei |
HiTrap TALON (cobalt) column chromatography | Plasmodium chabaudi |
HiTrap TALON (cobalt) column chromatography | Plasmodium vivax |
HiTrap TALON (cobalt) column chromatography | Plasmodium falciparum |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
gametocyte | - |
Plasmodium berghei | - |
gametocyte | - |
Plasmodium chabaudi | - |
gametocyte | - |
Plasmodium vivax | - |
gametocyte | - |
Plasmodium falciparum | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + FAM-GRTGRRNSI-NH2 | - |
Plasmodium berghei | ADP + phosphorylated FAM-GRTGRRNSI-NH2 | - |
? | |
ATP + FAM-GRTGRRNSI-NH2 | - |
Plasmodium chabaudi | ADP + phosphorylated FAM-GRTGRRNSI-NH2 | - |
? | |
ATP + FAM-GRTGRRNSI-NH2 | - |
Plasmodium vivax | ADP + phosphorylated FAM-GRTGRRNSI-NH2 | - |
? | |
ATP + FAM-GRTGRRNSI-NH2 | - |
Plasmodium falciparum | ADP + phosphorylated FAM-GRTGRRNSI-NH2 | - |
? | |
ATP + FAM-GRTGRRNSI-NH2 | - |
Plasmodium vivax Salvador | ADP + phosphorylated FAM-GRTGRRNSI-NH2 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
cyclic GMP-dependent protein kinase | - |
Plasmodium berghei |
cyclic GMP-dependent protein kinase | - |
Plasmodium chabaudi |
cyclic GMP-dependent protein kinase | - |
Plasmodium vivax |
cyclic GMP-dependent protein kinase | - |
Plasmodium falciparum |
PKG | - |
Plasmodium berghei |
PKG | - |
Plasmodium chabaudi |
PKG | - |
Plasmodium vivax |
PKG | - |
Plasmodium falciparum |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00000013 | - |
wild type enzyme, at pH 7.4 and 25°C | Plasmodium falciparum | N-(cyclopropylmethyl)-4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | |
0.00000016 | - |
wild type enzyme, at pH 7.4 and 25°C | Plasmodium falciparum | N-[5-(3-[2-[(cyclopropylmethyl)amino]pyrimidin-4-yl]-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl)-2-fluorophenyl]methanesulfonamide | |
0.00000045 | - |
wild type enzyme, at pH 7.4 and 25°C | Plasmodium falciparum | 4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | |
0.00000079 | - |
wild type enzyme, at pH 7.4 and 25°C | Plasmodium falciparum | 4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | |
0.00000079 | - |
wild type enzyme, at pH 7.4 and 25°C | Plasmodium falciparum | N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | |
0.00000088 | - |
wild type enzyme, at pH 7.4 and 25°C | Plasmodium falciparum | 4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | |
0.00000119 | - |
wild type enzyme, at pH 7.4 and 25°C | Plasmodium falciparum | N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | |
0.00000171 | - |
wild type enzyme, at pH 7.4 and 25°C | Plasmodium falciparum | 4-[2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | |
0.0000031 | - |
wild type enzyme, at pH 7.4 and 25°C | Plasmodium falciparum | 4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-yl]pyrimidin-2-amine | |
0.00000434 | - |
wild type enzyme, at pH 7.4 and 25°C | Plasmodium falciparum | N-(3-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]phenyl)methanesulfonamide | |
0.000231 | - |
mutant enzyme T618Q, at pH 7.4 and 25°C | Plasmodium falciparum | 4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)-6-methylimidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | |
0.000842 | - |
mutant enzyme T618Q, at pH 7.4 and 25°C | Plasmodium falciparum | 4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | |
0.001713 | - |
mutant enzyme T618Q, at pH 7.4 and 25°C | Plasmodium falciparum | 4-[2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-N-[4-(piperazin-1-yl)phenyl]pyrimidin-2-amine | |
0.0084 | - |
mutant enzyme T618Q, at pH 7.4 and 25°C | Plasmodium falciparum | 4-[7-[(dimethylamino)methyl]-2-(4-fluorophenyl)imidazo[1,2-a]pyridine-3-yl]pyrimidin-2-amine | |
0.02954 | - |
mutant enzyme T618Q, at pH 7.4 and 25°C | Plasmodium falciparum | N-[5-(3-[2-[(cyclopropylmethyl)amino]pyrimidin-4-yl]-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl)-2-fluorophenyl]methanesulfonamide | |
0.0525 | - |
mutant enzyme T618Q, at pH 7.4 and 25°C | Plasmodium falciparum | N-(cyclopropylmethyl)-4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | |
0.0737 | - |
mutant enzyme T618Q, at pH 7.4 and 25°C | Plasmodium falciparum | N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide | |
0.1 | - |
IC50 above 0.1 mM, mutant enzyme T618Q, at pH 7.4 and 25°C | Plasmodium falciparum | 4-[7-[(dimethylamino)methyl]-2-[3-(methanesulfonyl)phenyl]imidazo[1,2-a]pyridin-3-yl]pyrimidin-2-amine | |
0.1 | - |
IC50 above 0.1 mM, mutant enzyme T618Q, at pH 7.4 and 25°C | Plasmodium falciparum | N-(3-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]phenyl)methanesulfonamide | |
0.1 | - |
IC50 above 0.1 mM, mutant enzyme T618Q, at pH 7.4 and 25°C | Plasmodium falciparum | N-(5-[3-(2-aminopyrimidin-4-yl)-7-[(dimethylamino)methyl]-6-methylimidazo[1,2-a]pyridin-2-yl]-2-fluorophenyl)methanesulfonamide |