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Literature summary for 2.7.6.2 extracted from

  • Eschbach, M.L.; Mueller, I.B.; Gilberger, T.W.; Walter, R.D.; Wrenger, C.
    The human malaria parasite Plasmodium falciparum expresses an atypical N-terminally extended pyrophosphokinase with specificity for thiamine (2006), Biol. Chem., 387, 1583-1591.
    View publication on PubMed

Application

Application Comment Organism
medicine Malaria is a devastating and quite often deadly parasitic disease, resulting in significant public health problems in the tropics. The inevitable emergence of drug-resistant forms requires the continuous discovery and development of new antimalarials. These drugs should only target the parasite, with only harmless or no effects on the human host. Thus, ideal drug targets would be peculiarities in the parasite metabolism, such as vitamin B1 and B6 biosyntheses that are absent in its host. Plasmodium falciparum

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.062
-
pyrithiamine
-
Plasmodium falciparum
0.073
-
thiamine thiamine monophosphate is not accepted Plasmodium falciparum
1.1
-
ATP
-
Plasmodium falciparum

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ Optimal activity obtained by addition of 2-4 mM Mg2+. Plasmodium falciparum
Mn2+ Substitution of magnesium by Mn2+ decreases the enzyme activity by 42%. Plasmodium falciparum
Zn2+ Substitution of magnesium by Zn2+ decreases the enzyme activity by 85%. Plasmodium falciparum

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
38000
-
for PfTPK3, SDS-PAGE analysis followed by Western blotting Plasmodium falciparum
43000
-
for PfTPK2, SDS-PAGE analysis followed by Western blotting Plasmodium falciparum
47000
-
for PfTPK, SDS-PAGE analysis followed by Western blotting Plasmodium falciparum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
thiamine + ATP Saccharomyces cerevisiae
-
thiamine diphosphate + AMP
-
?
thiamine + ATP Schizosaccharomyces pombe
-
thiamine diphosphate + AMP
-
?
thiamine + ATP Plasmodium falciparum
-
thiamine diphosphate + AMP
-
?

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum
-
-
-
Saccharomyces cerevisiae
-
-
-
Schizosaccharomyces pombe
-
-
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
0.009
-
PfTPK3, with 4 mM magnesium ions in the enzyme assay Plasmodium falciparum
0.017
-
PfTPK2, with 4 mM magnesium ions in the enzyme assay Plasmodium falciparum
0.017
-
substrate: pyrithiamine, PfTPK Plasmodium falciparum
0.027
-
PfTPK, with 4 mM magnesium ions in the enzyme assay Plasmodium falciparum
999
-
no activity with thiochrome Plasmodium falciparum

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
pyrithiamine + ATP its specific activity is 30% lower in comparison to its natural substrate thiamine Plasmodium falciparum pyrithiamine diphosphate + AMP
-
?
thiamine + ATP
-
Saccharomyces cerevisiae thiamine diphosphate + AMP
-
?
thiamine + ATP
-
Schizosaccharomyces pombe thiamine diphosphate + AMP
-
?
thiamine + ATP
-
Plasmodium falciparum thiamine diphosphate + AMP
-
?

Subunits

Subunits Comment Organism
dimer gel filtration using a calibrated Superdex S-200 column Plasmodium falciparum

Synonyms

Synonyms Comment Organism
Plasmodium falciparum thiamine pyrophosphokinase
-
Plasmodium falciparum
pyrophosphokinase
-
Saccharomyces cerevisiae
pyrophosphokinase
-
Schizosaccharomyces pombe
pyrophosphokinase
-
Plasmodium falciparum
thiamine pyrophosphokinase
-
Saccharomyces cerevisiae
thiamine pyrophosphokinase
-
Schizosaccharomyces pombe
thiamine pyrophosphokinase
-
Plasmodium falciparum

Temperature Optimum [°C]

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

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8.5
-
PfTPK Plasmodium falciparum