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Literature summary extracted from

  • Low, H.; Chua, C.S.; Sim, T.-S.
    Plasmodium falciparum possesses a unique dual-specificity serine/threonine and tyrosine kinase, Pfnek3 (2012), Cell. Mol. Life Sci., 69, 1523-1535.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.12.2 additional information the enzyme is activated by phosphorylation through a specific mitogen-activated protein kinase kinase kinase Plasmodium falciparum

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.12.2 recombinant expression of GST-tagged wild-type and mutant Pfnek3 enzymes in Escherichia coli strain BL21 Plasmodium falciparum

Protein Variants

EC Number Protein Variants Comment Organism
2.7.12.2 additional information construction of a catalytically inactive enzyme knockout mutant DELTAPfnek3. The truncated Pfnek3 gene, encoding a catalytically active form of Pfnek3, is cloned into the GST-encoding pGEX-6P-1 vector Plasmodium falciparum
2.7.12.2 Y117D site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities Plasmodium falciparum
2.7.12.2 Y117E site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities Plasmodium falciparum
2.7.12.2 Y117F site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities. Reduction in tyrosine autophosphorylation is concomitant with the decrease in kinase activities for the Y117F, Y122F, and Y172F mutants Plasmodium falciparum
2.7.12.2 Y122D site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities Plasmodium falciparum
2.7.12.2 Y122E site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities Plasmodium falciparum
2.7.12.2 Y122F site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities. Reduction in tyrosine autophosphorylation is concomitant with the decrease in kinase activities for the Y117F, Y122F, and Y172F mutants Plasmodium falciparum
2.7.12.2 Y172D site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities Plasmodium falciparum
2.7.12.2 Y172E site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities Plasmodium falciparum
2.7.12.2 Y172F site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities. Reduction in tyrosine autophosphorylation is concomitant with the decrease in kinase activities for the Y117F, Y122F, and Y172F mutants Plasmodium falciparum
2.7.12.2 Y238D site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities Plasmodium falciparum
2.7.12.2 Y238E site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities Plasmodium falciparum
2.7.12.2 Y238F site-directed mutagenesis, inactive mutant Plasmodium falciparum
2.7.12.2 Y286F site-directed mutagenesis, inactive mutant Plasmodium falciparum
2.7.12.2 Y99F site-directed mutagenesis, the mutation leads to drastic reductions in both Pfnek3 tyrosine phosphorylation and catalytic activities Plasmodium falciparum

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.12.2 Mg2+ required Plasmodium falciparum
2.7.12.2 Mn2+ highly activating, more effective than Mg2+ Plasmodium falciparum
2.7.12.2 additional information serine/threonine and tyrosine kinase activities are distinctly influenced by Mg2+ and Mn2+ cofactors. Pfnek3 can undergo further tyrosine autophosphorylation in vitro, with Mn2+ as the preferred metal cofactor Plasmodium falciparum

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.12.2 ATP + myelin basic protein Plasmodium falciparum Pfnek3 phosphorylates MBP on threonine, but not serine residues ADP + phosphorylated myelin basic protein
-
?
2.7.12.2 ATP + Pfmap2 Plasmodium falciparum the enzyme phosphorylates its potential in vivo Pfmap2 substrate largely on Thr290 ADP + phosphorylated Pfmap2
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.7.12.2 Plasmodium falciparum
-
-
-

Posttranslational Modification

EC Number Posttranslational Modification Comment Organism
2.7.12.2 phosphoprotein the enzyme is activated by tyroaisne phosphorylation through a specific mitogen-activated protein kinase kinase kinase. Tyrosine residues Y117, Y122, Y172, and Y238 are proposed as phosphorylation sites essential for mediating the catalytic activities of Pfnek3 Plasmodium falciparum

Purification (Commentary)

EC Number Purification (Comment) Organism
2.7.12.2 recombinant GST-tagged wild-type and mutant Pfnek3 enzymes from Escherichia coli strain BL21 by glutathione affinity chromatography Plasmodium falciparum

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.12.2 ATP + myelin basic protein Pfnek3 phosphorylates MBP on threonine, but not serine residues Plasmodium falciparum ADP + phosphorylated myelin basic protein
-
?
2.7.12.2 ATP + Pfmap2 the enzyme phosphorylates its potential in vivo Pfmap2 substrate largely on Thr290 Plasmodium falciparum ADP + phosphorylated Pfmap2
-
?
2.7.12.2 additional information the enzyme displays both serine/threonine and tyrosine kinase activities in autophosphorylation reactions as well as in phosphorylation of the exogenous myelin basic protein substrate. Ability of Pfnek3 to autophosphorylate on both the serine/threonine and the tyrosine residues. The dual-specificity activity of the kinase is distinctly influenced by the type of divalent cation present Plasmodium falciparum ?
-
?

Synonyms

EC Number Synonyms Comment Organism
2.7.12.2 MAPKK
-
Plasmodium falciparum
2.7.12.2 Pfnek3
-
Plasmodium falciparum

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.7.12.2 30
-
assay at Plasmodium falciparum

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.12.2 7.2
-
assay at Plasmodium falciparum

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.12.2 ATP
-
Plasmodium falciparum

General Information

EC Number General Information Comment Organism
2.7.12.2 additional information Pfnek3 is a novel dual-specificity kinase of the malarial parasite, displaying both serine/threonine and tyrosine kinase activities, even though it has a HGDLKSTN motif in the catalytic loop that resembles the consensus HRDLKxxN signature found in the serine/threonine kinases. Tyrosine phosphorylation is involved in regulation of the serine/threonine and tyrosine kinase activities of Pfnek3 Plasmodium falciparum