PDBsum entry 4b2d

Transferase

PDB id: 4b2d

Contents

Protein chain

518 a.a.

Ligands

SER ×4

FBP ×4

Metals

_MG ×2

Waters ×1243

References listed in PDB file

Key reference

• Title: Serine is a natural ligand and allosteric activator of pyruvate kinase m2.
• Authors: B.Chaneton, P.Hillmann, L.Zheng, A.C.Martin, O.D.Maddocks, A.Chokkathukalam, J.E.Coyle, A.Jankevics, F.P.Holding, K.H.Vousden, C.Frezza, M.O'Reilly, E.Gottlieb.
• Ref.: Nature, 2012, 491, 458-462.
• PubMed id: 23064226

Abstract

Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation. Specifically, they overexpress the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of serine and glycine. Here we describe a new rheostat-like mechanistic relationship between PKM2 activity and serine biosynthesis. We show that serine can bind to and activate human PKM2, and that PKM2 activity in cells is reduced in response to serine deprivation. This reduction in PKM2 activity shifts cells to a fuel-efficient mode in which more pyruvate is diverted to the mitochondria and more glucose-derived carbon is channelled into serine biosynthesis to support cell proliferation.