Application | Comment | Organism |
---|---|---|
drug development | hypoxanthine-guanine phosphoribosyltransferase is an excellent target for antimalarial drug discovery | Plasmodium falciparum |
Crystallization (Comment) | Organism |
---|---|
purified recombinant enzyme PvHGPRT in complex with inhibitor [3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine, 21 mg/ml protein is incubated with 6.4 mM inhibitor on ice for 5 min, hanging drop method, mixing of 0.001 ml of protein and inhibitor with 0.001 ml of reservoir solution containing 0.3 M potassium thiocyanate, 0.1 M Bis-tris propane, pH 8.5, 18°C, X-ray diffraction structure determination and analysis at 2.85 A resolution, molecular replacement using the protein coordinates of subunit A of human HGPRT in complex with [(2-[(guanin-9H-yl)methyl]-propane-1,3-diyl)bis(oxy)]bis-(methylene)diphosphonic acid as template (PDB ID 4IJQ), model building | Plasmodium falciparum |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(2-[(3R,4R)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-[(2R)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-2-oxoethyl)phosphonic acid | enzyme-bound crystal structure analysis | Homo sapiens | |
(2-[(3R,4R)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-[(2R)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-2-oxoethyl)phosphonic acid | enzyme-bound crystal structure analysis; enzyme-bound crystal structure analysis | Plasmodium falciparum | |
(2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl)phosphonic acid | - |
Homo sapiens | |
(2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl)phosphonic acid | - |
Plasmodium falciparum | |
(S)-3-(guanin-9-yl)-pyrrolidin-N-ylacetylphosphonic acid | - |
Homo sapiens | |
(S)-3-(guanin-9-yl)-pyrrolidin-N-ylacetylphosphonic acid | - |
Plasmodium falciparum | |
additional information | design of Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase inhibitors as potential antimalarial therapeutics, rational structure-based methods, binding structure and comparison to the human enzyme, overview | Homo sapiens | |
additional information | design of Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase inhibitors as potential antimalarial therapeutics, rational structure-based methods, overview; design of Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase inhibitors as potential antimalarial therapeutics, rational structure-based methods, overview | Plasmodium falciparum | |
[(1S)-1-hydroxy-2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl]phosphonic acid | - |
Homo sapiens | |
[(1S)-1-hydroxy-2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl]phosphonic acid | - |
Plasmodium falciparum | |
[3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine | - |
Homo sapiens | |
[3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine | - |
Plasmodium falciparum |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate | Homo sapiens | - |
GMP + diphosphate | - |
? | |
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate | Plasmodium falciparum | - |
GMP + diphosphate | - |
? | |
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate | Homo sapiens | - |
IMP + diphosphate | - |
? | |
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate | Plasmodium falciparum | - |
IMP + diphosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P00492 | - |
- |
Plasmodium falciparum | A0A1G4HBT9 | - |
- |
Plasmodium falciparum | Q8IJS1 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate | - |
Homo sapiens | GMP + diphosphate | - |
? | |
guanosine + 5-phospho-alpha-D-ribose 1-diphosphate | - |
Plasmodium falciparum | GMP + diphosphate | - |
? | |
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate | - |
Homo sapiens | IMP + diphosphate | - |
? | |
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate | - |
Plasmodium falciparum | IMP + diphosphate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
HG[X]PRT | - |
Plasmodium falciparum |
hypoxanthine-guanine phosphoribosyltransferase | - |
Homo sapiens |
hypoxanthine-guanine phosphoribosyltransferase | - |
Plasmodium falciparum |
hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase | - |
Plasmodium falciparum |
More | cf. EC 2.4.2.22 | Plasmodium falciparum |
PvHGPRT | - |
Homo sapiens |
PvHGPRT | - |
Plasmodium falciparum |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0000013 | - |
[(1S)-1-hydroxy-2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl]phosphonic acid | pH not specified in the publication, 37°C | Homo sapiens | |
0.000002 | - |
[(1S)-1-hydroxy-2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl]phosphonic acid | pH not specified in the publication, 37°C | Plasmodium falciparum | |
0.000003 | - |
[3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine | pH not specified in the publication, 37°C | Homo sapiens | |
0.000006 | - |
[(1S)-1-hydroxy-2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl]phosphonic acid | pH not specified in the publication, 37°C | Plasmodium falciparum | |
0.000007 | - |
[3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine | pH not specified in the publication, 37°C | Plasmodium falciparum | |
0.000008 | - |
(2-[(3R,4R)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-[(2R)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-2-oxoethyl)phosphonic acid | pH not specified in the publication, 37°C | Homo sapiens | |
0.000008 | - |
[3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine | pH not specified in the publication, 37°C | Plasmodium falciparum | |
0.00001 | - |
(2-[(3R,4R)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-[(2R)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-2-oxoethyl)phosphonic acid | pH not specified in the publication, 37°C | Plasmodium falciparum | |
0.000014 | - |
(2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl)phosphonic acid | pH not specified in the publication, 37°C | Plasmodium falciparum | |
0.00002 | - |
[3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine | pH not specified in the publication, 37°C | Homo sapiens | |
0.00006 | - |
(2-[(3R,4R)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-[(2R)-2-hydroxy-2-phosphonoethoxy]pyrrolidin-1-yl]-2-oxoethyl)phosphonic acid | pH not specified in the publication, 37°C | Plasmodium falciparum | |
0.00008 | - |
(2-[[(3R,4R)-4-(6-oxo-1,6-dihydro-9H-purin-9-yl)-1-(phosphonoacetyl)pyrrolidin-3-yl]oxy]ethyl)phosphonic acid | pH not specified in the publication, 37°C | Plasmodium falciparum | |
0.0004 | - |
(S)-3-(guanin-9-yl)-pyrrolidin-N-ylacetylphosphonic acid | pH not specified in the publication, 37°C | Plasmodium falciparum | |
0.0026 | - |
(S)-3-(guanin-9-yl)-pyrrolidin-N-ylacetylphosphonic acid | pH not specified in the publication, 37°C | Plasmodium falciparum | |
0.073 | - |
(S)-3-(guanin-9-yl)-pyrrolidin-N-ylacetylphosphonic acid | pH not specified in the publication, 37°C | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | the activity of hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase, HG[X]PRT is essential for the growth of Plasmodium parasites | Plasmodium falciparum |