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Literature summary for 2.4.2.8 extracted from

  • Lee, C.C.; Medrano, F.J.; Craig, S.P., 3rd; Eakin, A.E.
    Investigation of the functional role of active site loop II in a hypoxanthine phosphoribosyltransferase (2001), Biochim. Biophys. Acta, 1537, 63-70.
    View publication on PubMed

Application

Application Comment Organism
medicine potential target for antiparasitic chemotherapy Homo sapiens
medicine potential target for antiparasitic chemotherapy Trypanosoma cruzi

Cloned(Commentary)

Cloned (Comment) Organism
functional expression of wild-type and loop II-deletion mutant in Escherichia coli Trypanosoma cruzi

Protein Variants

Protein Variants Comment Organism
additional information
-
Homo sapiens
additional information construction of deletion mutant lacking 7 amino acid residues, Y82-S88, of the active site loop II, resulting in highly reduced kcat-values and in increased Km-values for the substrates Trypanosoma cruzi

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information
-
Homo sapiens
additional information
-
additional information Km-values, loop II-deletion mutant Trypanosoma cruzi
0.0086
-
hypoxanthine wild-type enzyme Trypanosoma cruzi
0.012
-
guanine wild-type enzyme Trypanosoma cruzi
0.027
-
inosine monophosphate wild-type enzyme Trypanosoma cruzi
0.032
-
5-phospho-alpha-D-ribose 1-diphosphate wild-type enzyme Trypanosoma cruzi
0.035
-
diphosphate wild-type enzyme Trypanosoma cruzi

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Mg2+ required Trypanosoma cruzi

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate Homo sapiens
-
IMP + diphosphate
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate Trypanosoma cruzi
-
IMP + diphosphate
-
?
additional information Trypanosoma cruzi salvage incorporation of exogenous purine nucleotides, no de novo synthesis ?
-
?
additional information Homo sapiens locus of Lesch-Nyhan syndrome, activator of the prodrugs 6-mercaptopurine and allopurinol ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Trypanosoma cruzi
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant wild-type enzyme and loop II-deletion mutant from Escherichia coli Trypanosoma cruzi

Reaction

Reaction Comment Organism Reaction ID
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate active site structure Trypanosoma cruzi
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate during catalysis a long flexible loop closes over the active site, functional role Trypanosoma cruzi

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
-
Homo sapiens
additional information
-
kinetics in forward and reverse reaction Trypanosoma cruzi

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
-
Homo sapiens GMP + diphosphate
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
-
Trypanosoma cruzi GMP + diphosphate
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
Homo sapiens IMP + diphosphate
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
Homo sapiens IMP + diphosphate
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
Trypanosoma cruzi IMP + diphosphate
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
Trypanosoma cruzi IMP + diphosphate
-
r
additional information
-
Homo sapiens ?
-
?
additional information forward reaction: transfer of the phosphoribosyl group to N9 position of 6-oxopurines Trypanosoma cruzi ?
-
?
additional information salvage incorporation of exogenous purine nucleotides, no de novo synthesis Trypanosoma cruzi ?
-
?
additional information locus of Lesch-Nyhan syndrome, activator of the prodrugs 6-mercaptopurine and allopurinol Homo sapiens ?
-
?

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.001
-
inosine monophosphate loop II-deletion mutant Trypanosoma cruzi
0.002
-
diphosphate loop II-deletion mutant Trypanosoma cruzi
0.039
-
guanine loop II-deletion mutant Trypanosoma cruzi
0.05
-
5-phospho-alpha-D-ribose 1-diphosphate loop II-deletion mutant Trypanosoma cruzi
0.06
-
hypoxanthine loop II-deletion mutant Trypanosoma cruzi
0.472
-
inosine monophosphate wild-type enzyme Trypanosoma cruzi
0.477
-
diphosphate wild-type enzyme Trypanosoma cruzi
22.9
-
hypoxanthine wild-type enzyme Trypanosoma cruzi
23.2
-
5-phospho-alpha-D-ribose 1-diphosphate wild-type enzyme Trypanosoma cruzi
32.9
-
guanine wild-type enzyme Trypanosoma cruzi