4B2D

human PKM2 with L-serine and FBP bound.

Summary for 4B2D

• Entry DOI: 10.2210/pdb4b2d/pdb
• Related: 1T5A
• Descriptor: PYRUVATE KINASE ISOZYMES M1/M2, SERINE, 1,6-di-O-phosphono-beta-D-fructofuranose, ... (6 entities in total)
• Functional Keywords: transferase, tumour, pkm2, glycolysis
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 241156.73

Authors

Chaneton, B.,Hillmann, P.,Zheng, L.,Martin, A.C.L.,Maddocks, O.D.K.,Chokkathukalam, A.,Coyle, J.E.,Jankevics, A.,Holding, F.P.,Vousden, K.H.,Frezza, C.,O'Reilly, M.,Gottlieb, E. (deposition date: 2012-07-13, release date: 2012-10-10, Last modification date: 2023-12-20)

Primary citation

Chaneton, B.,Hillmann, P.,Zheng, L.,Martin, A.C.L.,Maddocks, O.D.K.,Chokkathukalam, A.,Coyle, J.E.,Jankevics, A.,Holding, F.P.,Vousden, K.H.,Frezza, C.,O'Reilly, M.,Gottlieb, E.
Serine is a natural ligand and allosteric activator of pyruvate kinase M2.
Nature, 491:458-462, 2012

PubMed 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.

PubMed: 23064226
DOI: 10.1038/nature11540

Experimental method

X-RAY DIFFRACTION (2.3 Å)