Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.7.11.11 extracted from

  • Wurtz, N.; Chapus, C.; Desplans, J.; Parzy, D.
    cAMP-dependent protein kinase from Plasmodium falciparum: an update (2011), Parasitology, 138, 1-25.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
6-benzyl-cAMP activator of PfPKA catalytic subunit Plasmodium falciparum
cAMP binding of 2 cAMP molecules to each regulatory subunit alters its affinity for the catalytic subunit, resulting in release of the active catalytic subunit Plasmodium falciparum

Application

Application Comment Organism
drug development the enzyme represents an attractive target for the development of anti-malarial drugs Plasmodium falciparum

Cloned(Commentary)

Cloned (Comment) Organism
gene pfpkac encoding the catalytic subunit, phylogenetic analysis Plasmodium falciparum
gene pfpkar encoding the regulatory subunit, phylogenetic analysis and sequence comparison Plasmodium falciparum

Inhibitors

Inhibitors Comment Organism Structure
H89 inhibits PfPKA catalytic subunit activity in vitro, leads to parasite growth arrest and morphological alteration; inhibits PfPKA catalytic subunit activity in vitro, leads to parasite growth arrest and morphological alteration Plasmodium falciparum
imatinib competes for the ATP binding site; competes for the ATP binding site Plasmodium falciparum
protein kinase inhibitor PKI, a natural endogenous inhibitor; PKI, a natural endogenous inhibitor Plasmodium falciparum

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
Plasmodium falciparum 5829
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Plasmodium falciparum

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
42200
-
alpha2beta2, 2 * 42200, about, catalytic subunit, + 2 * 50800, about, regulatory subunit, sequence calculation Plasmodium falciparum
50800
-
alpha2beta2, 2 * 42200, about, catalytic subunit, + 2 * 50800, about, regulatory subunit, sequence calculation Plasmodium falciparum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Plasmodium falciparum the PKA catalytic subunit a serine/threonine kinase, that can phosphorylate many substrates, such as additional protein kinases and transcription factors ?
-
?

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum Q7K6A0 catalytic subunit
-
Plasmodium falciparum Q7KQK0 regulatory subunit
-

Source Tissue

Source Tissue Comment Organism Textmining
additional information in cytosolic extracts of both the asexual and sexual stages of the parasite, catalytic and regulatory subunits of PfPKA are expressed weakly during the ring and trophozoite stages compared to the schizont stage, and pfpkac mRNA levels are lower in gametocytes and gametes Plasmodium falciparum
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information the PKA catalytic subunit a serine/threonine kinase, that can phosphorylate many substrates, such as additional protein kinases and transcription factors Plasmodium falciparum ?
-
?

Subunits

Subunits Comment Organism
heterotetramer alpha2beta2, 2 * 42200, about, catalytic subunit, + 2 * 50800, about, regulatory subunit, sequence calculation Plasmodium falciparum
More structure comparison with mammalian enzymes, overview Plasmodium falciparum

Synonyms

Synonyms Comment Organism
cyclic AMP-dependent protein kinase
-
Plasmodium falciparum
PKA
-
Plasmodium falciparum
protein kinase A
-
Plasmodium falciparum

Cofactor

Cofactor Comment Organism Structure
ATP residues of the PfPKA catalytic subunit G40, G42, and G45 are involved in ATP fixation, E82 in ATP stabiization, D175 in orienting the phosphate of ATP Plasmodium falciparum

pI Value

Organism Comment pI Value Maximum pI Value
Plasmodium falciparum regulatory subunit, sequence calculation
-
7.49
Plasmodium falciparum catalytic subunit, sequence calculation
-
9.11

General Information

General Information Comment Organism
malfunction downregulation of gene pfpkac mRNA using gene silencing leads to morphological changes in schizont stages and cell cycle arrest, and is also associated with a compensatory decrease in pfpkar mRNA levels, suggesting a transcriptional self-regulation of the PfPKA signalling network Plasmodium falciparum
metabolism the cAMP/PfPKA signalling pathway is essential for parasite growth and survival, mechanism and regulation, model of cAMP/PKA signalling pathway in Plasmodium falciparum, and of signalling events including PfPKA catalytic subunit during the Plasmodium falciparum life cycle, overview. The cAMP pathway regulates sporozoite motility and hepatic cell invasion by Plasmodium falciparum sporozoites. Putative role for PfPKA in the induction of gametocytogenesis, in erythrocyte invasion by merozoites, and in the regulation of mitochondrial protein traffic. Highly complex relationship between cAMP/PfPKA and calcium pathways in the asexual life cycle, with a key role of PfPKA in anion transport across the erythrocyte membrane, overview Plasmodium falciparum
additional information PKA has two regulatory subunits, which bind to and inhibit two catalytic subunits, domain organization and structure comparison with mammalian/human enzymes, overview. Sequence E221-C226-P227-P228-F229-Y23 and residue E161 of the PfPKA catalytic subunit are involved in substrate recognition, residues K63, D211, D157, N162, and E199 are required for catalysis Plasmodium falciparum
physiological function Plasmodium falciparum cAMP-dependent protein kinase plays an important role in the parasite's life cycle. The parasites appear to have tightly controlled mechanisms for selfregulating PfPKA levels to maintain appropriate PKA signalling Plasmodium falciparum