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Literature summary for 2.4.2.8 extracted from

  • Roy, S.; Karmakar, T.; Nagappa, L.K.; Prahlada Rao, V.S.; Balasubramanian, S.; Balaram, H.
    Role of W181 in modulating kinetic properties of Plasmodium falciparum hypoxanthine guanine xanthine phosphoribosyltransferase (2016), Proteins, 84, 1658-1669 .
    View publication on PubMed
Search for more literature for 2.4.2.8

Activating Compound

Activating Compound Comment Organism Structure
IMP activates the enzyme, activating effects on wild-type and mutant enzymes, overview. Upon activation of the mutants with IMP, the lag phase disappears, while an increase in the specific activity values appears. Although activation of wild-type and mutants by IMP increases their catalytic efficiency by about 100fold, it is found that the kcat/Km values for the mutants drop by 5.7 to 75fold when compared with the wild-type enzyme Plasmodium falciparum

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of wild-type and mutant enzymes in Escherichia coli strain Sphi609 Plasmodium falciparum

Protein Variants

Protein Variants Comment Organism
additional information molecular dynamics simulations of wild-type and in silico W181S, W181T, W181Y, and W181F PfHGXPRT mutants bound to IMP/PPi/Mg2+, overview. Escherichia coli strain Sphi609, (ara, DELTApro-gpt-lac, thi, hpt, pup, purH, J, strA) is a knockout strain for the genes encoding hypoxanthine phosphoribosyltransferase (HPRT) and xanthine-guanine phosphoribosyltransferase (XGPRT). Although activation of the enzyme mutants by IMP increases their catalytic efficiency by about 100fold, it is found that the kcat/Km values for the mutants drop by 5.7 to 75fold when compared with the wild-type enzyme Plasmodium falciparum
W181F site-directed mutagenesis of residue Trp181 in loop III', the mutant shows an over 5fold decreased xanthine phosphoribosylation activity compared to wild-type and an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) Plasmodium falciparum
W181S site-directed mutagenesis of residue Trp181 in loop III', the mutant shows an over 5fold decreased xanthine phosphoribosylation activity compared to wild-type and an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) Plasmodium falciparum
W181T site-directed mutagenesis of residue Trp181 in loop III', the mutant shows an over 10fold decreased xanthine phosphoribosylation activity compared to wild-type and an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) Plasmodium falciparum
W181Y site-directed mutagenesis of residue Trp181 in loop III', the mutant shows an over 5fold decreased xanthine phosphoribosylation activity compared to wild-type and an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) Plasmodium falciparum

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.025
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated wild-type enzyme Plasmodium falciparum
0.094
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181Y Plasmodium falciparum
0.233
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181F Plasmodium falciparum
0.251
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181S Plasmodium falciparum
1.084
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated wild-type enzyme Plasmodium falciparum
2.286
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181S Plasmodium falciparum
2.783
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181Y Plasmodium falciparum
3.668
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181F Plasmodium falciparum

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required, binding structure, overview Plasmodium falciparum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
guanine + 5-phospho-alpha-D-ribose 1-diphosphate Plasmodium falciparum
-
 GMP + diphosphate
-
 ?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate Plasmodium falciparum
-
 IMP + diphosphate
-
 ?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate Plasmodium falciparum reaction of EC 2.4.2.22 XMP + diphosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum Q8IJS1
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
-
 Plasmodium falciparum GMP + diphosphate
-
 ?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
-
 Plasmodium falciparum IMP + diphosphate
-
 ?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate reaction of EC 2.4.2.22 Plasmodium falciparum XMP + diphosphate
-
 ?

Subunits

Subunits Comment Organism
More structure-function analysis, molecular dynamics, dynamic cross-correlation maps, and configurational entropy, overview Plasmodium falciparum

Synonyms

Synonyms Comment Organism
HGXPRT
-
 Plasmodium falciparum
hypoxanthine guanine xanthine phosphoribosyltransferase
-
 Plasmodium falciparum
More cf. EC 2.4.2.22 Plasmodium falciparum

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Plasmodium falciparum

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.1
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181F Plasmodium falciparum
0.1
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181Y Plasmodium falciparum
0.2
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181F Plasmodium falciparum
0.2
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated wild-type enzyme Plasmodium falciparum
0.32
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181S Plasmodium falciparum
0.5
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181Y Plasmodium falciparum
0.67
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181S Plasmodium falciparum
1.6
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated wild-type enzyme Plasmodium falciparum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Plasmodium falciparum

General Information

General Information Comment Organism
additional information out of the five active site loops (I, II, III, III', and IV) in PfHGXPRT, loop III' facilitates the closure of the hood over the core domain which is the penultimate step during enzymatic catalysis. Residue Trp181 is important. Molceluar dynamics and simulation, structure-activity analysis, overview Plasmodium falciparum
physiological function hypoxanthine-guanine-xanthine phosphoribosyltransference (HGXPRT) is a key enzyme in the purine salvage pathway of the malarial parasite, Plasmodium falciparum (Pf). It catalyses the conversion of hypoxanthine, guanine, and xanthine to their corresponding mononucleotides; IMP, GMP, and XMP, respectively Plasmodium falciparum

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.036
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181Y Plasmodium falciparum
0.055
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181F Plasmodium falciparum
0.14
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181S Plasmodium falciparum
0.185
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated wild-type enzyme Plasmodium falciparum
0.43
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181F Plasmodium falciparum
2.67
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181S Plasmodium falciparum
5.32
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181Y Plasmodium falciparum
64
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated wild-type enzyme Plasmodium falciparum