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Literature summary for 1.1.1.44 extracted from

  • Haeussler, K.; Fritz-Wolf, K.; Reichmann, M.; Rahlfs, S.; Becker, K.
    Characterization of Plasmodium falciparum 6-phosphogluconate dehydrogenase as an antimalarial drug target (2018), J. Mol. Biol., 430, 4049-4067 .
    View publication on PubMed
Search for more literature for 1.1.1.44

Cloned(Commentary)

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 (Commentary)

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

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

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 [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 [Da] Molecular Weight Maximum [Da] Comment Organism
79000
-
 gel filtration Homo sapiens
79000
-
 gel filtration Plasmodium falciparum

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens P52209
-
-
Plasmodium falciparum Q8IKT2
-
-
Plasmodium falciparum Q8IKT2 isolate 3D7
-

Posttranslational Modification

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 (Commentary)

Purification (Comment) Organism
-
 Homo sapiens
-
 Plasmodium falciparum

Specific Activity [micromol/min/mg]

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

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 and Products (Substrate)

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

Subunits Comment Organism
homodimer
-
 Homo sapiens
homodimer
-
 Plasmodium falciparum

Synonyms

Synonyms Comment Organism
6-phosphogluconate dehydrogenase
-
 Homo sapiens
6-phosphogluconate dehydrogenase
-
 Plasmodium falciparum
6PGD
-
 Homo sapiens
6PGD
-
 Plasmodium falciparum

Turnover Number [1/s]

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

Cofactor Comment Organism Structure
NADP+
-
 Homo sapiens
NADP+
-
 Plasmodium falciparum

IC50 Value

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

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