Pyruvate kinase M2 (PKM2) catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate. It plays a central role in the metabolic reprogramming of cancer cells and is expressed in most human tumors. It is essential in indiscriminate proliferation, …

Structural studies reveal that small molecule activators bind PKM2 at the subunit interaction interface, a site distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP).

2008年3月13日 · Using a novel proteomic screen for phosphotyrosine-binding proteins, we have made the observation that an enzyme involved in glycolysis, the human M2 (fetal) isoform of pyruvate kinase (PKM2),...

2019年6月26日 · TEPP-46 and FBP, the allosteric activators that induce PKM2 tetramerization limits PKM2 methylation. Importantly, PKM2 activity remains unaltered by methylation; however, methylated PKM2 reprograms the metabolic phenotype toward aerobic glycolysis from oxidative phosphorylation to support tumor cell proliferation, migration, and metastasis [ 161 ].

Biochemical and structural analyses demonstrate that PKM2 Y105E (phosphorylation mimic of Y105) decreases pyruvate kinase activity by inhibiting FBP (fructose 1,6-bisphosphate)-induced R-state formation, and PKM2 K305Q (acetylation mimic of K305) abolishes the activity by hindering tetramer formation.

Residues 482 and 489 are components of the FBP-activation loop that are predicted to interact with FBP but not F1P. b, Purified recombinant PKM2 (rPKM2) was incubated with the indicated...

2024年2月8日 · When the position Y105 of PKM2 is phosphorylated, it can inhibit the binding of PKM2 to allosteric activator FBP, thereby inhibiting the formation of PKM2 tetramer and oxidative phosphorylation. In turn, this increases the production of lactate which promotes the proliferation of tumor cells [ 22 ].