Cloned (Comment) | Organism |
---|---|
expression of His-tagged enzymes in Escherichia coli M15 cells | Homo sapiens |
expression of His-tagged enzymes in Escherichia coli M15 cells | Plasmodium falciparum |
overexpression in Escherichia coli M15 | Homo sapiens |
overexpression in Escherichia coli M15 | Plasmodium falciparum |
Crystallization (Comment) | Organism |
---|---|
crystals are grown at 22 °C in hanging drops or sitting drops with the vapor diffusion technique. X-ray structures of the enzyme in native form as well as in complex with 6-phosphogluconate or NADP+ at resolutions of 2.8 A, 1.9 A, and 2.9 A. A flexible loop close to the active site rearranges upon binding of 6-phosphogluconate and likely regulates the conformation of the cofactor NADP | Plasmodium falciparum |
crystals are grown at 22°C in hanging drops with the vapor diffusion technique. X-ray structures of Pf6PGD in native form as well as in complex with 6-phospho-D-gluconate or NADP+ at resolutions of 2.8 A, 1.9 A, and 2.9 A, respectively | Plasmodium falciparum |
Protein Variants | Comment | Organism |
---|---|---|
W104L | all kinetic parameters, especially the KM-value for 6-phospho-D-gluconate, are decreased in the mutant | Plasmodium falciparum |
W104L | all kinetic parameters, especially the KM-value for 6-phosphogluconate, are decreased in the mutant | Plasmodium falciparum |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(5Z)-5-[[4-(3-fluorophenoxy)phenyl]methylidene]-2-imino-3-(2-methoxyphenyl)-1,3-thiazolidin-4-one | - |
Homo sapiens | |
(5Z)-5-[[4-(3-fluorophenoxy)phenyl]methylidene]-2-imino-3-(2-methoxyphenyl)-1,3-thiazolidin-4-one | - |
Plasmodium falciparum | |
11-(4-methoxyphenyl)-11H-benzo[b]indeno[1,2-e][1,4]thiazepin-12-ol | - |
Homo sapiens | |
11-(4-methoxyphenyl)-11H-benzo[b]indeno[1,2-e][1,4]thiazepin-12-ol | - |
Plasmodium falciparum | |
2,6-dimethoxy-4-[5-phenyl-4-[4-(phenylsulfanyl)phenyl]-1H-imidazol-2-yl]phenol | - |
Homo sapiens | |
2,6-dimethoxy-4-[5-phenyl-4-[4-(phenylsulfanyl)phenyl]-1H-imidazol-2-yl]phenol | - |
Plasmodium falciparum | |
2-methyl-3-[2-(3-nitrophenyl)-2-oxoethyl]naphthalene-1,4-dione | - |
Homo sapiens | |
2-methyl-3-[2-(3-nitrophenyl)-2-oxoethyl]naphthalene-1,4-dione | - |
Plasmodium falciparum | |
4,4'-[1,4-phenylenebis(oxy-1H-benzimidazole-6,2-diyl)]dianiline | - |
Homo sapiens | |
4,4'-[1,4-phenylenebis(oxy-1H-benzimidazole-6,2-diyl)]dianiline | - |
Plasmodium falciparum | |
5,5'-methylenebis[2-(4-methoxyphenyl)-1H-benzimidazole] | - |
Homo sapiens | |
5,5'-methylenebis[2-(4-methoxyphenyl)-1H-benzimidazole] | - |
Plasmodium falciparum | |
5,6-bis(2H-1,3-benzodioxol-5-yl)-2-(3-methylphenyl)-4,7-diphenyl-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3,8(2H)-trione | - |
Homo sapiens | |
5,6-bis(2H-1,3-benzodioxol-5-yl)-2-(3-methylphenyl)-4,7-diphenyl-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3,8(2H)-trione | - |
Plasmodium falciparum | |
7-[[3-(benzyloxy)phenyl][(4-methylpyridin-2-yl)amino]methyl]quinolin-8-ol | - |
Homo sapiens | |
7-[[3-(benzyloxy)phenyl][(4-methylpyridin-2-yl)amino]methyl]quinolin-8-ol | - |
Plasmodium falciparum | |
MMV000563 | - |
Homo sapiens | |
MMV000563 | - |
Plasmodium falciparum | |
MMV000720 | - |
Homo sapiens | |
MMV000720 | - |
Plasmodium falciparum | |
MMV007199 | - |
Homo sapiens | |
MMV007199 | - |
Plasmodium falciparum | |
MMV007228 | - |
Homo sapiens | |
MMV007228 | - |
Plasmodium falciparum | |
MMV007273 | - |
Homo sapiens | |
MMV007273 | - |
Plasmodium falciparum | |
MMV007384 | - |
Homo sapiens | |
MMV007384 | - |
Plasmodium falciparum | |
MMV011895 | - |
Homo sapiens | |
MMV011895 | - |
Plasmodium falciparum | |
MMV665972 | - |
Homo sapiens | |
MMV665972 | - |
Plasmodium falciparum | |
MMV666125 | - |
Homo sapiens | |
MMV666125 | - |
Plasmodium falciparum | |
N-[(4-chlorophenyl)(2-hydroxy-1-naphthyl)methyl]-2-phenylacetamide | - |
Homo sapiens | |
N-[(4-chlorophenyl)(2-hydroxy-1-naphthyl)methyl]-2-phenylacetamide | - |
Plasmodium falciparum |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0048 | - |
NADP+ | pH 8.0, 25°C, mutant enzyme W104L | Plasmodium falciparum | |
0.0058 | - |
6-phospho-D-gluconate | pH 8.0, 25°C, mutant enzyme W104L | Plasmodium falciparum | |
0.0069 | - |
NADP+ | pH 8.0, 25°C, wild-type enzyme | Homo sapiens | |
0.009 | - |
NADP+ | pH 8.0, 25°C, wild-type enzyme | Plasmodium falciparum | |
0.0113 | - |
6-phospho-D-gluconate | pH 8.0, 25°C, wild-type enzyme | Plasmodium falciparum | |
0.0337 | - |
6-phospho-D-gluconate | pH 8.0, 25°C, wild-type enzyme | Homo sapiens | |
6.9 | - |
NADP+ | pH 8.0, 25°C | Homo sapiens | |
33.7 | - |
6-phospho-D-gluconate | pH 8.0, 25°C | Homo sapiens |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
79000 | - |
gel filtration | Homo sapiens |
79000 | - |
gel filtration | Plasmodium falciparum |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
6-phospho-D-gluconate + NADP+ | Homo sapiens | - |
D-ribulose 5-phosphate + CO2 + NADPH + H+ | - |
? | |
6-phospho-D-gluconate + NADP+ | Plasmodium falciparum | - |
D-ribulose 5-phosphate + CO2 + NADPH + H+ | - |
? | |
6-phospho-D-gluconate + NADP+ | Homo sapiens | the enzyme catalyzes a step of the pentose phosphate pathway | D-ribulose 5-phosphate + CO2 + NADPH + H+ | - |
? | |
6-phospho-D-gluconate + NADP+ | Plasmodium falciparum | the enzyme catalyzes a step of the pentose phosphate pathway | D-ribulose 5-phosphate + CO2 + NADPH + H+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P52209 | - |
- |
Plasmodium falciparum | Q8IKT2 | - |
- |
Plasmodium falciparum | Q8IKT2 | isolate 3D7 | - |
Posttranslational Modification | Comment | Organism |
---|---|---|
nitrosylation | the activity of the enzyme (Pf6PGD) is posttranslationally redox regulated via S-nitrosylation | Plasmodium falciparum |
nitrosylation | the activity of the enzyme is posttranslationally redox regulated via S-nitrosylation | Plasmodium falciparum |
Purification (Comment) | Organism |
---|---|
- |
Homo sapiens |
- |
Plasmodium falciparum |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
5.7 | - |
pH 8.0, 25°C, mutant enzyme W104L | Plasmodium falciparum |
8 | - |
pH 8.0, 25°C, wild-type enzyme | Plasmodium falciparum |
22.1 | - |
pH 8.0, 25°C | Homo sapiens |
22.1 | - |
pH 8.0, 25°C, wild-type enzyme | Homo sapiens |
Storage Stability | Organism |
---|---|
-80°C, 50% glycerol, stable for at least one month | Homo sapiens |
-80°C, 50% glycerol, stable for at least one month | Plasmodium falciparum |
-80°C, 50% glycerol, under long-term storage conditions , the enzyme is stable for at least one month | Plasmodium falciparum |
-80°C, 50% glycerol, under long-term storage conditions, the enzyme is stable for at least one month | Homo sapiens |
4°C, up to 5 days, stable | Homo sapiens |
4°C, up to 5 days, stable | Plasmodium falciparum |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
6-phospho-D-gluconate + NADP+ | - |
Homo sapiens | D-ribulose 5-phosphate + CO2 + NADPH + H+ | - |
? | |
6-phospho-D-gluconate + NADP+ | - |
Plasmodium falciparum | D-ribulose 5-phosphate + CO2 + NADPH + H+ | - |
? | |
6-phospho-D-gluconate + NADP+ | the enzyme catalyzes a step of the pentose phosphate pathway | Homo sapiens | D-ribulose 5-phosphate + CO2 + NADPH + H+ | - |
? | |
6-phospho-D-gluconate + NADP+ | the enzyme catalyzes a step of the pentose phosphate pathway | Plasmodium falciparum | D-ribulose 5-phosphate + CO2 + NADPH + H+ | - |
? |
Subunits | Comment | Organism |
---|---|---|
homodimer | - |
Homo sapiens |
homodimer | - |
Plasmodium falciparum |
Synonyms | Comment | Organism |
---|---|---|
6-phosphogluconate dehydrogenase | - |
Homo sapiens |
6-phosphogluconate dehydrogenase | - |
Plasmodium falciparum |
6PGD | - |
Homo sapiens |
6PGD | - |
Plasmodium falciparum |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
5.2 | - |
6-phospho-D-gluconate | mutant enzyme W104L, pH 8.0, 25°C | Plasmodium falciparum | |
5.2 | - |
6-phospho-D-gluconate | pH 8.0, 25°C, mutant enzyme W104L | Plasmodium falciparum | |
5.7 | - |
NADP+ | mutant enzyme W104L, pH 8.0, 25°C | Plasmodium falciparum | |
5.7 | - |
NADP+ | pH 8.0, 25°C, mutant enzyme W104L | Plasmodium falciparum | |
7.1 | - |
6-phospho-D-gluconate | pH 8.0, 25°C, wild-type enzyme | Plasmodium falciparum | |
7.1 | - |
6-phospho-D-gluconate | wild-type enzyme, pH 8.0, 25°C | Plasmodium falciparum | |
7.6 | - |
NADP+ | pH 8.0, 25°C, wild-type enzyme | Plasmodium falciparum | |
7.6 | - |
NADP+ | wild-type enzyme, pH 8.0, 25°C | Plasmodium falciparum | |
21.4 | - |
NADP+ | pH 8.0, 25°C | Homo sapiens | |
21.4 | - |
NADP+ | pH 8.0, 25°C, wild-type enzyme | Homo sapiens | |
22.2 | - |
6-phospho-D-gluconate | pH 8.0, 25°C | Homo sapiens | |
22.2 | - |
6-phospho-D-gluconate | pH 8.0, 25°C, wild-type enzyme | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADP+ | - |
Homo sapiens | |
NADP+ | - |
Plasmodium falciparum |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0013 | - |
pH 8.0, 25°C | Homo sapiens | MMV007199 | |
0.0013 | - |
25°C, pH 8.0 | Homo sapiens | (5Z)-5-[[4-(3-fluorophenoxy)phenyl]methylidene]-2-imino-3-(2-methoxyphenyl)-1,3-thiazolidin-4-one | |
0.0016 | - |
pH 8.0, 25°C | Plasmodium falciparum | MMV011895 | |
0.0016 | - |
25°C, pH 8.0 | Plasmodium falciparum | 4,4'-[1,4-phenylenebis(oxy-1H-benzimidazole-6,2-diyl)]dianiline | |
0.0018 | - |
pH 8.0, 25°C | Plasmodium falciparum | MMV007228 | |
0.0018 | - |
pH 8.0, 25°C | Homo sapiens | MMV007273 | |
0.0018 | - |
25°C, pH 8.0 | Homo sapiens | 2,6-dimethoxy-4-[5-phenyl-4-[4-(phenylsulfanyl)phenyl]-1H-imidazol-2-yl]phenol | |
0.0018 | - |
25°C, pH 8.0 | Plasmodium falciparum | 5,6-bis(2H-1,3-benzodioxol-5-yl)-2-(3-methylphenyl)-4,7-diphenyl-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3,8(2H)-trione | |
0.0021 | - |
pH 8.0, 25°C | Plasmodium falciparum | MMV007273 | |
0.0021 | - |
pH 8.0, 25°C | Homo sapiens | MMV011895 | |
0.0021 | - |
25°C, pH 8.0 | Plasmodium falciparum | 2,6-dimethoxy-4-[5-phenyl-4-[4-(phenylsulfanyl)phenyl]-1H-imidazol-2-yl]phenol | |
0.0021 | - |
25°C, pH 8.0 | Homo sapiens | 4,4'-[1,4-phenylenebis(oxy-1H-benzimidazole-6,2-diyl)]dianiline | |
0.0022 | - |
pH 8.0, 25°C | Homo sapiens | MMV000720 | |
0.0022 | - |
25°C, pH 8.0 | Homo sapiens | 7-[[3-(benzyloxy)phenyl][(4-methylpyridin-2-yl)amino]methyl]quinolin-8-ol | |
0.0024 | - |
pH 8.0, 25°C | Homo sapiens | MMV007384 | |
0.0024 | - |
25°C, pH 8.0 | Homo sapiens | 5,5'-methylenebis[2-(4-methoxyphenyl)-1H-benzimidazole] | |
0.0025 | - |
pH 8.0, 25°C | Plasmodium falciparum | MMV007384 | |
0.0025 | - |
25°C, pH 8.0 | Plasmodium falciparum | 5,5'-methylenebis[2-(4-methoxyphenyl)-1H-benzimidazole] | |
0.0027 | - |
pH 8.0, 25°C | Homo sapiens | MMV007228 | |
0.0027 | - |
pH 8.0, 25°C | Plasmodium falciparum | MMV666125 | |
0.0027 | - |
25°C, pH 8.0 | Plasmodium falciparum | 2-methyl-3-[2-(3-nitrophenyl)-2-oxoethyl]naphthalene-1,4-dione | |
0.0027 | - |
25°C, pH 8.0 | Homo sapiens | 5,6-bis(2H-1,3-benzodioxol-5-yl)-2-(3-methylphenyl)-4,7-diphenyl-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3,8(2H)-trione | |
0.0029 | - |
pH 8.0, 25°C | Plasmodium falciparum | MMV007199 | |
0.0029 | - |
25°C, pH 8.0 | Plasmodium falciparum | (5Z)-5-[[4-(3-fluorophenoxy)phenyl]methylidene]-2-imino-3-(2-methoxyphenyl)-1,3-thiazolidin-4-one | |
0.0031 | - |
pH 8.0, 25°C | Plasmodium falciparum | MMV000720 | |
0.0031 | - |
25°C, pH 8.0 | Plasmodium falciparum | 7-[[3-(benzyloxy)phenyl][(4-methylpyridin-2-yl)amino]methyl]quinolin-8-ol | |
0.0035 | - |
pH 8.0, 25°C | Homo sapiens | MMV000563 | |
0.0035 | - |
25°C, pH 8.0 | Homo sapiens | 11-(4-methoxyphenyl)-11H-benzo[b]indeno[1,2-e][1,4]thiazepin-12-ol | |
0.004 | - |
pH 8.0, 25°C | Plasmodium falciparum | MMV665972 | |
0.004 | - |
25°C, pH 8.0 | Plasmodium falciparum | N-[(4-chlorophenyl)(2-hydroxy-1-naphthyl)methyl]-2-phenylacetamide | |
0.0042 | - |
pH 8.0, 25°C | Plasmodium falciparum | MMV000563 | |
0.0042 | - |
25°C, pH 8.0 | Plasmodium falciparum | 11-(4-methoxyphenyl)-11H-benzo[b]indeno[1,2-e][1,4]thiazepin-12-ol | |
0.0043 | - |
pH 8.0, 25°C | Homo sapiens | MMV665972 | |
0.0043 | - |
25°C, pH 8.0 | Homo sapiens | N-[(4-chlorophenyl)(2-hydroxy-1-naphthyl)methyl]-2-phenylacetamide | |
0.0049 | - |
pH 8.0, 25°C | Homo sapiens | MMV666125 | |
0.0049 | - |
25°C, pH 8.0 | Homo sapiens | 2-methyl-3-[2-(3-nitrophenyl)-2-oxoethyl]naphthalene-1,4-dione |
General Information | Comment | Organism |
---|---|---|
drug target | Plasmodium falciparum 6-phosphogluconate dehydrogenase is an antimalarial drug target | Plasmodium falciparum |
drug target | the enzyme is an attractive antimalarial drug target due to its central role in metabolism | Plasmodium falciparum |
metabolism | the enzyme catalyzes a step of the pentose phosphate pathway | Homo sapiens |
metabolism | the enzyme catalyzes a step of the pentose phosphate pathway | Plasmodium falciparum |
physiological function | the NADPH produced by 6PGD is crucial for antioxidant defense and redox regulation and ribose 5-phosphate is essential for DNA and RNA synthesis in the rapidly growing parasite | Plasmodium falciparum |