4GWK

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

4GWK の概要

• エントリーDOI: 10.2210/pdb4gwk/pdb
• 関連するPDBエントリー: 2JKV 4GWG
• 分子名称: 6-phosphogluconate dehydrogenase, decarboxylating, 3-PHOSPHOGLYCERIC ACID, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• 機能のキーワード: 6-phosphogluconate dehydrogenase, 3-phosphoglycerate, dehydrogenase, nadp, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): P52209
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 54037.43

構造登録者

He, C.,Zhou, L.,Zhang, L. (登録日: 2012-09-03, 公開日: 2012-11-28, 最終更新日: 2023-09-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.534 Å)