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Succinyl-5-aminoimidazole-4-carboxamide-1-ribose 5'-Phosphate (SAICAR) Activates Pyruvate Kinase Isoform M2 (PKM2) in Its Dimeric Form.

Biochemistry.. 2016-08; 
Yan M, Chakravarthy S, Tokuda JM, Pollack L, Bowman GD, Lee YS.
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Mutagenesis Services ... form. EXPERIMENTAL PROCEDURES Materials Plasmid encoding GST-PKM2 in pGEX-6P-1 vector (GE Life Sciences) was custom synthesized by GenScript. Oligonucleotides were synthesized by Operon. Site directed mutagenesis ... Get A Quote

摘要

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. This perceived inactivity has fueled controversy about how the dimeric form of pyruvate kinase might contribute to cancer. Here we investigate enzymatic properties of PKM2(G415R), a variant derived from a cancer patient, which we show by size-exclusion chromatography and small-angle X-ray scattering to be a dimer that cannot form a tetramer in solution. Although PKM2(G415R) binds to fructose 1,6-bisphosphate (FBP), unlike the wild type this PKM2 variant shows no activation by FBP. In contrast, ... More

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