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Literature summary 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

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.4.2.8 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
2.4.2.22 IMP
-
 Plasmodium falciparum

Cloned(Commentary)

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

Protein Variants

EC Number Protein Variants Comment Organism
2.4.2.8 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
2.4.2.8 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
2.4.2.8 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
2.4.2.8 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
2.4.2.8 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
2.4.2.22 W181F the mutant retains its ability to catalyse the phosphoribosylation of hypoxanthine, guanine and xanthine, albeit with significantly lower specific activities than the wild type enzyme. The mutant shows an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate by 3.4fold under unactivated condition and a decrease in catalytic efficiency by 76fold under activated condition as compared to that of the wild type enzyme Plasmodium falciparum
2.4.2.22 W181S the mutant retains its ability to catalyse the phosphoribosylation of hypoxanthine, guanine and xanthine, albeit with significantly lower specific activities than the wild type enzyme. The mutant shows 10fold reduced xanthine phosphoribosylation activity compared to the wild type enzyme Plasmodium falciparum
2.4.2.22 W181S the mutant retains its ability to catalyze the phosphoribosylation of hypoxanthine, guanine and xanthine, albeit with significantly lower specific activities than the wild type enzyme. The mutant shows an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate by 2.1fold under unactivated condition and a decrease in catalytic efficiency by more than 11fold under activated condition as compared to that of the wild type enzyme Plasmodium falciparum
2.4.2.22 W181Y the mutant retains its ability to catalyse the phosphoribosylation of hypoxanthine, guanine and xanthine, albeit with significantly lower specific activities than the wild type enzyme. The mutant shows an increase in Km for 5-phospho-alpha-D-ribose 1-diphosphate by 2.6fold under unactivated condition and a decrease in catalytic efficiency by more than 5fold under activated condition as compared to that of the wild type enzyme Plasmodium falciparum

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.4.2.8 0.025
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated wild-type enzyme Plasmodium falciparum
2.4.2.8 0.094
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181Y Plasmodium falciparum
2.4.2.8 0.233
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181F Plasmodium falciparum
2.4.2.8 0.251
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181S Plasmodium falciparum
2.4.2.8 1.084
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated wild-type enzyme Plasmodium falciparum
2.4.2.8 2.286
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181S Plasmodium falciparum
2.4.2.8 2.783
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181Y Plasmodium falciparum
2.4.2.8 3.668
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181F Plasmodium falciparum
2.4.2.22 0.053
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated wild type enzyme, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.094
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated mutant enzyme W181Y, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.233
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated mutant enzyme W181F, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.251
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated mutant enzyme W181S, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 1.084
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated wild type enzyme, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 2.286
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated mutant enzyme W181S, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 2.783
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated mutant enzyme W181Y, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 3.668
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated mutant enzyme W181F, at pH 7.4, temperature not specified in the publication Plasmodium falciparum

Metals/Ions

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

Natural Substrates/ Products (Substrates)

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

Organism

EC Number Organism UniProt Comment Textmining
2.4.2.8 Plasmodium falciparum Q8IJS1
-
-
2.4.2.22 Plasmodium falciparum
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.4.2.22 Q-Sepharose column chromatography, CM Sepharose column chromatography and Sephacryl S-200 gel filtration Plasmodium falciparum

Substrates and Products (Substrate)

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

Subunits

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

Synonyms

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

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.4.2.8 37
-
 assay at Plasmodium falciparum

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.4.2.8 0.1
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181F Plasmodium falciparum
2.4.2.8 0.1
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181Y Plasmodium falciparum
2.4.2.8 0.2
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181F Plasmodium falciparum
2.4.2.8 0.2
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated wild-type enzyme Plasmodium falciparum
2.4.2.8 0.32
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181S Plasmodium falciparum
2.4.2.8 0.5
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181Y Plasmodium falciparum
2.4.2.8 0.67
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181S Plasmodium falciparum
2.4.2.8 1.6
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated wild-type enzyme Plasmodium falciparum
2.4.2.22 0.1
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated mutant enzyme W181F, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.1
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated mutant enzyme W181Y, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.2
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated mutant enzyme W181F, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.2
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated wild type enzyme, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.32
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated mutant enzyme W181S, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.5
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated mutant enzyme W181Y, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.67
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated mutant enzyme W181S, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 1.6
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated wild type enzyme, at pH 7.4, temperature not specified in the publication Plasmodium falciparum

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.4.2.8 7.4
-
 assay at Plasmodium falciparum

General Information

EC Number General Information Comment Organism
2.4.2.8 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
2.4.2.8 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]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.4.2.8 0.036
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181Y Plasmodium falciparum
2.4.2.8 0.055
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181F Plasmodium falciparum
2.4.2.8 0.14
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated mutant W181S Plasmodium falciparum
2.4.2.8 0.185
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant nonactivated wild-type enzyme Plasmodium falciparum
2.4.2.8 0.43
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181F Plasmodium falciparum
2.4.2.8 2.67
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181S Plasmodium falciparum
2.4.2.8 5.32
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated mutant W181Y Plasmodium falciparum
2.4.2.8 64
-
 5-phospho-alpha-D-ribose 1-diphosphate pH 7.4, 37°C, recombinant IMP-activated wild-type enzyme Plasmodium falciparum
2.4.2.22 0.36
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated mutant enzyme W181Y, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.4
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated mutant enzyme W181F, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 0.54
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated mutant enzyme W181F, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 1.39
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated mutant enzyme W181S, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 1.84
-
 5-phospho-alpha-D-ribose 1-diphosphate unactivated wild type enzyme, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 2.6
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated mutant enzyme W181S, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 5.3
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated mutant enzyme W181Y, at pH 7.4, temperature not specified in the publication Plasmodium falciparum
2.4.2.22 30.1
-
 5-phospho-alpha-D-ribose 1-diphosphate IMP-activated wild type enzyme, at pH 7.4, temperature not specified in the publication Plasmodium falciparum