4GWK

Crystal structure of 6-phosphogluconate dehydrogenase complexed with 3-phosphoglyceric acid

Summary for 4GWK

• Entry DOI: 10.2210/pdb4gwk/pdb
• Related: 2JKV 4GWG
• Descriptor: 6-phosphogluconate dehydrogenase, decarboxylating, 3-PHOSPHOGLYCERIC ACID, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: 6-phosphogluconate dehydrogenase, 3-phosphoglycerate, dehydrogenase, nadp, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): P52209
• Total number of polymer chains: 1
• Total formula weight: 54037.43

Authors

He, C.,Zhou, L.,Zhang, L. (deposition date: 2012-09-03, release date: 2012-11-28, Last modification date: 2023-09-13)

Primary citation

Hitosugi, T.,Zhou, L.,Elf, S.,Fan, J.,Kang, H.B.,Seo, J.H.,Shan, C.,Dai, Q.,Zhang, L.,Xie, J.,Gu, T.L.,Jin, P.,Aleckovic, M.,Leroy, G.,Kang, Y.,Sudderth, J.A.,Deberardinis, R.J.,Luan, C.H.,Chen, G.Z.,Muller, S.,Shin, D.M.,Owonikoko, T.K.,Lonial, S.,Arellano, M.L.,Khoury, H.J.,Khuri, F.R.,Lee, B.H.,Ye, K.,Boggon, T.J.,Kang, S.,He, C.,Chen, J.
Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth.
Cancer Cell, 22:585-600, 2012

PubMed Abstract: It is unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1), commonly upregulated in human cancers due to loss of TP53, contributes to biosynthesis regulation in part by controlling intracellular levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2-phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG activates 3-phosphoglycerate dehydrogenase to provide feedback control of 3-PG levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to significantly decreased glycolysis, PPP flux and biosynthesis, as well as attenuated cell proliferation and tumor growth.

PubMed: 23153533
DOI: 10.1016/j.ccr.2012.09.020

Experimental method

X-RAY DIFFRACTION (1.534 Å)