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Literature summary for 3.6.1.23 extracted from

  • Whittingham, J.L.; Leal, I.; Nguyen, C.; Kasinathan, G.; Bell, E.; Jones, A.F.; Berry, C.; Benito, A.; Turkenburg, J.P.; Dodson, E.J.; Perez, L.M.; Wilkinson, A.J.; Johansson, N.G.; Brun, R.; Gilbert, I.H.; Pacanowska, D.G.; Wilson, K.S.
    dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors (2005), Structure, 13, 329-338.
    View publication on PubMed
Search for more literature for 3.6.1.23

Application

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(Commentary)

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 (Commentary)

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

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 [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0024
-
 dUTP pH 5.7-6.2, recombinant enzyme Plasmodium falciparum

Localization

Localization Comment Organism GeneOntology No. Textmining
intracellular
-
 Plasmodium falciparum 5622
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
 Plasmodium falciparum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
dUTP + H2O Plasmodium falciparum
-
 dUMP + diphosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum
-
-
-

Purification (Commentary)

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

Source Tissue Comment Organism Textmining
schizont asexual stage Plasmodium falciparum
-
trophozoite proliferative intraerythroctic Plasmodium falciparum
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
25.75
-
 purified recombinant enzyme Plasmodium falciparum

Substrates and Products (Substrate)

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

Subunits Comment Organism
trimer crystal structure Plasmodium falciparum

Synonyms

Synonyms Comment Organism
deoxyuridine nucleotidohydrolase
-
 Plasmodium falciparum
dUTPase
-
 Plasmodium falciparum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
5.7 6.2 assay at Plasmodium falciparum

Ki Value [mM]

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

pI Value

Organism Comment pI Value Maximum pI Value
Plasmodium falciparum sequence calculation
-
 6.5

IC50 Value

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