Application | Comment | Organism |
---|---|---|
drug development | dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors | Plasmodium falciparum |
Cloned (Comment) | Organism |
---|---|
DNA and amino acid sequence determination and analysis, the gene locates on chromosome 11, overexpression in Escherichia coli strain BL21(DE3) | Plasmodium falciparum |
Crystallization (Comment) | Organism |
---|---|
purified recombinant enzyme in complex with inhibitor 2',3'-dideoxy-3'-fluoro-5'-O-trityluridine, X-ray diffraction structure determination and analysis at 2.4 A resolution | Plasmodium falciparum |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
2',3',5'-trideoxy-3'-fluoro-5'-(tritylamino)uridine | activity against the parasites with IC50: 0.0053 mM | Plasmodium falciparum | |
2',3'-dideoxy-3'-fluoro-5'-O-trityluridine | activity against the parasites with IC50: 0.0020 mM, binding structure involving Tyr112, Ile117, Ile108, and Asn103, overview | Plasmodium falciparum | |
2',5'-dideoxy-5'-(tritylamino)uridine | activity against the parasites with IC50: 0.0045 mM | Plasmodium falciparum | |
2'-deoxy-5'-O-(triphenylsilyl)uridine | activity against the parasites with IC50: 0.0011 mM | Plasmodium falciparum | |
2'-deoxy-5'-O-trityluridine | activity against the parasites with IC50: 0.006 mM | Plasmodium falciparum | |
2'-deoxy-5'-O-[tris(1-methylethoxy)silyl]uridine | activity against the parasites with IC50: 0.013 mM | Plasmodium falciparum |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0024 | - |
dUTP | pH 5.7-6.2, recombinant enzyme | Plasmodium falciparum |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
intracellular | - |
Plasmodium falciparum | 5622 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | - |
Plasmodium falciparum |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
dUTP + H2O | Plasmodium falciparum | - |
dUMP + diphosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Plasmodium falciparum | - |
- |
- |
Purification (Comment) | Organism |
---|---|
recombinant enzyme from Escherichia coli strain BL21(DE3) by cation exchange chromatography, gel filtration, and anion exchange chromatography to near homogeneity | Plasmodium falciparum |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
schizont | asexual stage | Plasmodium falciparum | - |
trophozoite | proliferative intraerythroctic | Plasmodium falciparum | - |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
25.75 | - |
purified recombinant enzyme | Plasmodium falciparum |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
dUTP + H2O | - |
Plasmodium falciparum | dUMP + diphosphate | - |
? | |
dUTP + H2O | the enzyme is highly specific for dUTP | Plasmodium falciparum | dUMP + diphosphate | - |
? |
Subunits | Comment | Organism |
---|---|---|
trimer | crystal structure | Plasmodium falciparum |
Synonyms | Comment | Organism |
---|---|---|
deoxyuridine nucleotidohydrolase | - |
Plasmodium falciparum |
dUTPase | - |
Plasmodium falciparum |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
5.7 | 6.2 | assay at | Plasmodium falciparum |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0002 | - |
2',5'-dideoxy-5'-(tritylamino)uridine | pH 5.7-6.2, recombinant enzyme | Plasmodium falciparum | |
0.0018 | - |
2'-deoxy-5'-O-trityluridine | pH 5.7-6.2, recombinant enzyme | Plasmodium falciparum | |
0.0028 | - |
2'-deoxy-5'-O-(triphenylsilyl)uridine | pH 5.7-6.2, recombinant enzyme | Plasmodium falciparum | |
0.005 | - |
2',3'-dideoxy-3'-fluoro-5'-O-trityluridine | pH 5.7-6.2, recombinant enzyme | Plasmodium falciparum | |
0.0125 | - |
2',3',5'-trideoxy-3'-fluoro-5'-(tritylamino)uridine | pH 5.7-6.2, recombinant enzyme | Plasmodium falciparum | |
0.2271 | - |
2'-deoxy-5'-O-[tris(1-methylethoxy)silyl]uridine | pH 5.7-6.2, recombinant enzyme | Plasmodium falciparum |
Organism | Comment | pI Value Maximum | pI Value |
---|---|---|---|
Plasmodium falciparum | sequence calculation | - |
6.5 |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0011 | - |
activity against the parasites with IC50: 0.0011 mM | Plasmodium falciparum | 2'-deoxy-5'-O-(triphenylsilyl)uridine | |
0.002 | - |
activity against the parasites with IC50: 0.0020 mM, binding structure involving Tyr112, Ile117, Ile108, and Asn103, overview | Plasmodium falciparum | 2',3'-dideoxy-3'-fluoro-5'-O-trityluridine | |
0.0045 | - |
activity against the parasites with IC50: 0.0045 mM | Plasmodium falciparum | 2',5'-dideoxy-5'-(tritylamino)uridine | |
0.0053 | - |
activity against the parasites with IC50: 0.0053 mM | Plasmodium falciparum | 2',3',5'-trideoxy-3'-fluoro-5'-(tritylamino)uridine | |
0.006 | - |
activity against the parasites with IC50: 0.006 mM | Plasmodium falciparum | 2'-deoxy-5'-O-trityluridine | |
0.013 | - |
activity against the parasites with IC50: 0.013 mM | Plasmodium falciparum | 2'-deoxy-5'-O-[tris(1-methylethoxy)silyl]uridine |