3X05

Crystal structure of PIP4KIIBETA T201M complex with AMP

3X05 の概要

• エントリーDOI: 10.2210/pdb3x05/pdb
• 関連するPDBエントリー: 3WZZ 3X01 3X02 3X03 3X04 3X06 3X07 3X08 3X09 3X0A 3X0B 3X0C
• 分子名称: Phosphatidylinositol 5-phosphate 4-kinase type-2 beta, ADENOSINE MONOPHOSPHATE (3 entities in total)
• 機能のキーワード: lipid kinase, phosphoinositide signaling, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane ; Peripheral membrane protein : P78356
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 91306.88

構造登録者

Takeuchi, K.,Lo, Y.H.,Sumita, K.,Senda, M.,Terakawa, J.,Dimitoris, A.,Locasale, J.W.,Sasaki, M.,Yoshino, H.,Zhang, Y.,Kahoud, E.R.,Takano, T.,Yokota, T.,Emerling, B.,Asara, J.A.,Ishida, T.,Shimada, I.,Daikoku, T.,Cantley, L.C.,Senda, T.,Sasaki, A.T. (登録日: 2014-10-09, 公開日: 2015-10-14, 最終更新日: 2023-11-08)

主引用文献

Sumita, K.,Lo, Y.H.,Takeuchi, K.,Senda, M.,Kofuji, S.,Ikeda, Y.,Terakawa, J.,Sasaki, M.,Yoshino, H.,Majd, N.,Zheng, Y.,Kahoud, E.R.,Yokota, T.,Emerling, B.M.,Asara, J.M.,Ishida, T.,Locasale, J.W.,Daikoku, T.,Anastasiou, D.,Senda, T.,Sasaki, A.T.
The Lipid Kinase PI5P4K beta Is an Intracellular GTP Sensor for Metabolism and Tumorigenesis
Mol.Cell, 61:187-198, 2016

PubMed Abstract: While cellular GTP concentration dramatically changes in response to an organism's cellular status, whether it serves as a metabolic cue for biological signaling remains elusive due to the lack of molecular identification of GTP sensors. Here we report that PI5P4Kβ, a phosphoinositide kinase that regulates PI(5)P levels, detects GTP concentration and converts them into lipid second messenger signaling. Biochemical analyses show that PI5P4Kβ preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation, and its activity reflects changes in direct proportion to the physiological GTP concentration. Structural and biological analyses reveal that the GTP-sensing activity of PI5P4Kβ is critical for metabolic adaptation and tumorigenesis. These results demonstrate that PI5P4Kβ is the missing GTP sensor and that GTP concentration functions as a metabolic cue via PI5P4Kβ. The critical role of the GTP-sensing activity of PI5P4Kβ in cancer signifies this lipid kinase as a cancer therapeutic target.

PubMed: 26774281
DOI: 10.1016/j.molcel.2015.12.011

実験手法

X-RAY DIFFRACTION (2.5 Å)