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Literature summary for 2.7.1.40 extracted from

  • Gehrig, S.; Macpherson, J.A.; Driscoll, P.C.; Symon, A.; Martin, S.R.; MacRae, J.I.; Kleinjung, J.; Fraternali, F.; Anastasiou, D.
    An engineered photoswitchable mammalian pyruvate kinase (2017), FEBS J., 284, 2955-2980 .
    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, molecular dynamics (MD) simulations of the human PKM2 (hPKM2) monomer in the absence (apo-hPKM2) or presence of FBP (hPKM2-FBP), the molecular dynamics simulations identify conformational changes in PKM2 associated with FBP binding, overview Homo sapiens
fructose 1,6-bisphosphate FBP, molecular dynamics simulations identify conformational changes in PKM2 associated with FBP binding Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information molecular dynamics simulations are used to guide the design of mPKM2 internal light/oxygen/voltage-sensitive domain 2 (LOV2) fusion at position D24 (PiL[D24]), resulting in an engineered pyruvate kinase M2 (PKM2) variant that harbours an insertion of the light-sensing LOV2 domain from Avena Sativa within a region implicated in allosteric regulation by fructose 1,6-bisphosphate (FBP). The LOV2 photoreaction is preserved in the PiL[D24] chimera and causes secondary structure changes that are associated with a 30% decrease in the Km of the enzyme for phosphoenolpyruvate resulting in increased pyruvate kinase activity after light exposure. Importantly, this change in activity is reversible upon light withdrawal. Expression of PiL[D24] in cells leads to light-induced increase in labelling of pyruvate from glucose. Light induces a reversible increase in the enzymatic activity of purified PiL[D24]. Steady-state Michaelis-Menten kinetic parameters for PiL[D24] under dark and lit conditions determined by NMR spectroscopy at 21°C Mus musculus

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Mg2+ required Mus musculus

Organism

Organism UniProt Comment Textmining
Homo sapiens P14618
-
-
Mus musculus P52480
-
-

Source Tissue

Source Tissue Comment Organism Textmining
muscle
-
 Homo sapiens
-
muscle
-
 Mus musculus
-

Synonyms

Synonyms Comment Organism
hPKM2
-
 Homo sapiens
mPKM2
-
 Mus musculus

General Information

General Information Comment Organism
malfunction aberrant growth factor signalling and oxidative stress inhibit PKM2, which results in the diversion of glucose carbons into anabolic and redox regulating pathways that are essential for cell growth and survival. Proliferating PKM2-null tumour cells have no detectable PK expression, which likely reflects an adaptation that suppresses expression of PKM1 in these tumours. Consistent with a negative role of high PK activity in tumour growth, both exogenous expression of PKM1 or pharmacological activators that overcome endogenous PKM2-inhibiting mechanisms impede tumour growth by increasing cellular PK activity, effectively rendering endogenous PKM2 into a PKM1-like enzyme Homo sapiens
malfunction aberrant growth factor signalling and oxidative stress inhibit PKM2, which results in the diversion of glucose carbons into anabolic and redox regulating pathways that are essential for cell growth and survival. Proliferating PKM2-null tumour cells have no detectable PK expression, which likely reflects an adaptation that suppresses expression of PKM1 in these tumours. Consistent with a negative role of high PK activity in tumour growth, both exogenous expression of PKM1 or pharmacological activators that overcome endogenous PKM2-inhibiting mechanisms impede tumour growth by increasing cellular PK activity, effectively rendering endogenous PKM2 into a PKM1-like enzyme Mus musculus
additional information molecular dynamics (MD) simulations of the human PKM2 (hPKM2) monomer in the absence (apo-hPKM2) or presence of FBP (hPKM2-FBP), analysis of the mechanical response of PKM2 upon binding of FBP, overview Homo sapiens
physiological function various intracellular mechanisms in cancer cells maintain PKM2 in a low-activity monomeric state and forced stabilisation of tetrameric PKM2 increases its enzymatic activity thereby impeding cell proliferation Homo sapiens
physiological function various intracellular mechanisms in cancer cells maintain PKM2 in a low-activity monomeric state and forced stabilisation of tetrameric PKM2 increases its enzymatic activity thereby impeding cell proliferation Mus musculus