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Literature summary for 2.4.2.8 extracted from

  • Wenck, M.A.; Medrano, F.J.; Eakin, A.E.; Craig, S.P.
    Steady-state kinetics of the hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi (2004), Biochim. Biophys. Acta, 1700, 11-18.
    View publication on PubMed

Application

Application Comment Organism
pharmacology the enzyme is a target for mechanism-based design of specific inhibitors Trypanosoma cruzi

Inhibitors

Inhibitors Comment Organism Structure
5-phospho-alpha-D-ribose 1-diphosphate competitive versus diphosphate and GMP or IMP Trypanosoma cruzi
diphosphate competitive versus 5-phospho-alpha-D-ribose 1-diphosphate, uncompetitive versus hypoxanthine or guanine Trypanosoma cruzi
GMP competitive versus 5-phospho-alpha-D-ribose 1-diphosphate, noncompetitive versus guanine Trypanosoma cruzi
IMP competitive versus 5-phospho-alpha-D-ribose 1-diphosphate, noncompetitive versus hypoxanthine Trypanosoma cruzi
additional information product inhibition study, the substrates/products protect the enzyme against digestion by trypsin, especially hypoxanthine with diphosphate Trypanosoma cruzi

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information steady-state kinetics and dissociation constants Trypanosoma cruzi
0.0086
-
hypoxanthine pH 7.5, 37°C, recombinant wild-type enzyme Trypanosoma cruzi
0.012
-
guanine pH 7.5, 37°C, recombinant wild-type enzyme Trypanosoma cruzi
0.016
-
IMP pH 7.5, 37°C, recombinant wild-type enzyme Trypanosoma cruzi
0.016
-
diphosphate pH 7.5, 37°C, recombinant wild-type enzyme, with IMP Trypanosoma cruzi
0.022
-
diphosphate pH 7.5, 37°C, recombinant wild-type enzyme, with GMP Trypanosoma cruzi
0.029
-
GMP pH 7.5, 37°C, recombinant wild-type enzyme Trypanosoma cruzi
0.031
-
5-phospho-alpha-D-ribose 1-diphosphate pH 7.5, 37°C, recombinant wild-type enzyme, with hypoxanthine Trypanosoma cruzi
0.032
-
5-phospho-alpha-D-ribose 1-diphosphate pH 7.5, 37°C, recombinant wild-type enzyme, with guanine Trypanosoma cruzi

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+
-
Trypanosoma cruzi

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
GMP + diphosphate Trypanosoma cruzi
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
-
r
IMP + diphosphate Trypanosoma cruzi
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
r

Organism

Organism UniProt Comment Textmining
Trypanosoma cruzi
-
-
-

Reaction

Reaction Comment Organism Reaction ID
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate ordered bi bi reaction mechanism, formation of dead-end complexes with purine substrates and diphosphate Trypanosoma cruzi

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
-
Trypanosoma cruzi

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GMP + diphosphate
-
Trypanosoma cruzi guanine + 5-phospho-alpha-D-ribose 1-diphosphate
-
r
IMP + diphosphate
-
Trypanosoma cruzi hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
r
additional information formation of dead-end complexes with purine substrates and diphosphate Trypanosoma cruzi ?
-
?

Synonyms

Synonyms Comment Organism
HPRT
-
Trypanosoma cruzi

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Trypanosoma cruzi

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.09
-
GMP pH 7.5, 37°C, recombinant enzyme Trypanosoma cruzi
0.1
-
diphosphate pH 7.5, 37°C, recombinant enzyme, with GMP Trypanosoma cruzi
0.46
-
IMP pH 7.5, 37°C, recombinant enzyme Trypanosoma cruzi
0.47
-
diphosphate pH 7.5, 37°C, recombinant enzyme, with IMP Trypanosoma cruzi
22.9
-
hypoxanthine pH 7.5, 37°C, recombinant enzyme Trypanosoma cruzi
23.2
-
5-phospho-alpha-D-ribose 1-diphosphate pH 7.5, 37°C, recombinant enzyme, with hypoxanthine Trypanosoma cruzi
32.2
-
5-phospho-alpha-D-ribose 1-diphosphate pH 7.5, 37°C, recombinant enzyme, with guanine Trypanosoma cruzi
32.9
-
guanine pH 7.5, 37°C, recombinant enzyme Trypanosoma cruzi

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Trypanosoma cruzi

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.02
-
GMP pH 7.5, 37°C, product inhibition versus 5-phospho-alpha-D-ribose 1-diphosphate, substrate guanine, recombinant enzyme Trypanosoma cruzi
0.037
-
IMP pH 7.5, 37°C, product inhibition versus 5-phospho-alpha-D-ribose 1-diphosphate, substrate hypoxanthine, recombinant enzyme Trypanosoma cruzi
0.037
-
5-phospho-alpha-D-ribose 1-diphosphate pH 7.5, 37°C, product inhibition versus IMP, substrate hypoxanthine, recombinant enzyme Trypanosoma cruzi
0.093
-
diphosphate pH 7.5, 37°C, product inhibition versus 5-phospho-alpha-D-ribose 1-diphosphate, substrate guanine, recombinant enzyme Trypanosoma cruzi
0.1
-
GMP pH 7.5, 37°C, product inhibition versus guanine, substrate guanine, recombinant enzyme Trypanosoma cruzi
0.122
-
diphosphate pH 7.5, 37°C, product inhibition versus 5-phospho-alpha-D-ribose 1-diphosphate, substrate hypoxanthine, recombinant enzyme Trypanosoma cruzi
0.122
-
diphosphate pH 7.5, 37°C, product inhibition versus hypoxanthine, substrate hypoxanthine, recombinant enzyme Trypanosoma cruzi
0.138
-
5-phospho-alpha-D-ribose 1-diphosphate pH 7.5, 37°C, product inhibition versus diphosphate, substrate hypoxanthine, recombinant enzyme Trypanosoma cruzi
0.138
-
IMP pH 7.5, 37°C, product inhibition versus hypoxanthine, substrate hypoxanthine, recombinant enzyme Trypanosoma cruzi
0.298
-
5-phospho-alpha-D-ribose 1-diphosphate pH 7.5, 37°C, product inhibition versus diphosphate, substrate guanine, recombinant enzyme Trypanosoma cruzi
0.302
-
diphosphate pH 7.5, 37°C, product inhibition versus guanine, substrate guanine, recombinant enzyme Trypanosoma cruzi
0.423
-
5-phospho-alpha-D-ribose 1-diphosphate pH 7.5, 37°C, product inhibition versus GMP, substrate guanine, recombinant enzyme Trypanosoma cruzi