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

BRENDA support

Literature summary for 2.7.1.40 extracted from

  • Yan, M.; Chakravarthy, S.; Tokuda, J.M.; Pollack, L.; Bowman, G.D.; Lee, Y.S.
    Succinyl-5-aminoimidazole-4-carboxamide-1-ribose 5-phosphate (SAICAR) activates pyruvate kinase isoform M2 (PKM2) in its dimeric form (2016), Biochemistry, 55, 4731-4736 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.1.40

Activating Compound

Activating Compound Comment Organism Structure
fructose 1,6-bisphosphate FBP, FBP-mediated PKM2 activation requires the tetramerization of PKM2. The dimeric enzyme, e.g. mutant PKM2G415R, is in its tense form and cannot be activated by FBP Homo sapiens
additional information different modes of PKM2 activation by FBP and SAICAR, schematic overview Homo sapiens
succinyl-5-aminoimidazole-4-carboxamide-1-ribose 5'-phosphate SAICAR, an endogenous metabolite that correlates with an increased level of cell proliferation, it activates pyruvate kinase isoform M2 (PKM2) in its dimeric form, connection between SAICAR binding and the oligomeric state of PKM2, SAICAR stimulates the PKM2 dimer without inducing formation of a PKM2 tetramer. SAICAR binds to PKM2 mutant G415R better than it binds to wild-type PKM2 Homo sapiens

Protein Variants

Protein Variants Comment Organism
G415R site-directed mutagenesis, the mutant binds fructose 1,6-bisphosphate, but is not activated by it, unlike the wild-type PKM2. But the mutant is activated by succinyl-5-aminoimidazole-4-carboxamide-1-ribose 5'-phosphate (SAICAR) Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.25
-
 ADP mutant PKM2G415R, pH 7.6, 37°C Homo sapiens
1.2
-
 phosphoenolpyruvate mutant PKM2G415R, pH 7.6, 37°C Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ADP + phosphoenolpyruvate Homo sapiens
-
 ATP + pyruvate
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P14618
-
-

Source Tissue

Source Tissue Comment Organism Textmining
carcinoma cell prevalence of dimeric PKM2 in cancer Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ADP + phosphoenolpyruvate
-
 Homo sapiens ATP + pyruvate
-
 ?

Subunits

Subunits Comment Organism
dimer dimeric PKM2 is regarded as an inactive form of tetrameric pyruvate kinase, but the enzymatic activity of the PKM2 dimer is determined in presence of metabolite SAICAR Homo sapiens
More although found to exist in different oligomeric forms in cells, like other pyruvate kinases, PKM2 is considered to have maximal pyruvate kinase activity as a tetramer. Prevalence of dimeric PKM2 in cancer Homo sapiens
tetramer
-
 Homo sapiens

Synonyms

Synonyms Comment Organism
PKM2
-
 Homo sapiens
pyruvate kinase isoform M2
-
 Homo sapiens
pyruvate kinase M2
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.57
-
 phosphoenolpyruvate mutant PKM2G415R, pH 7.6, 37°C Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.6
-
 assay at Homo sapiens

General Information

General Information Comment Organism
physiological function human pyruvate kinase isoform M2 (PKM2) is a glycolytic enzyme isoform implicated in cancer. Malignant cancer cells have higher levels of dimeric PKM2, which is regarded as an inactive form of tetrameric pyruvate kinase. The enzymatic activity of the PKM2 dimer likely has a key role in cancer progression. In addition to its classical role in generating ATP from ADP and the phosphate donor PEP, PKM2 also has been found to phosphorylate protein substrates Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.475
-
 phosphoenolpyruvate mutant PKM2G415R, pH 7.6, 37°C Homo sapiens