7EM7

Crystal structure of the PI5P4Kbeta N203D-XTP complex

7EM7 の概要

• エントリーDOI: 10.2210/pdb7em7/pdb
• 分子名称: Phosphatidylinositol 5-phosphate 4-kinase type-2 beta, [(2~{R},3~{S},4~{R},5~{R})-5-[2,6-bis(oxidanylidene)-3~{H}-purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl phosphono hydrogen phosphate, [[(2~{R},3~{S},4~{R},5~{R})-5-[2,6-bis(oxidanylidene)-3~{H}-purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] phosphono hydrogen phosphate (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)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 90828.13

構造登録者

Senda, M.,Senda, T. (登録日: 2021-04-13, 公開日: 2022-03-30, 最終更新日: 2023-11-29)

主引用文献

Takeuchi, K.,Ikeda, Y.,Senda, M.,Harada, A.,Okuwaki, K.,Fukuzawa, K.,Nakagawa, S.,Yu, H.Y.,Nagase, L.,Imai, M.,Sasaki, M.,Lo, Y.H.,Ito, D.,Osaka, N.,Fujii, Y.,Sasaki, A.T.,Senda, T.
The GTP responsiveness of PI5P4K beta evolved from a compromised trade-off between activity and specificity.
Structure, 30:886-899.e4, 2022

PubMed Abstract: Unlike most kinases, phosphatidylinositol 5-phosphate 4-kinase β (PI5P4Kβ) utilizes GTP as a physiological phosphate donor and regulates cell growth under stress (i.e., GTP-dependent stress resilience). However, the genesis and evolution of its GTP responsiveness remain unknown. Here, we reveal that PI5P4Kβ has acquired GTP preference by generating a short dual-nucleotide-recognizing motif called the guanine efficient association (GEA) motif. Comparison of nucleobase recognition with 660 kinases and 128 G proteins has uncovered that most kinases and PI5P4Kβ use their main-chain atoms for adenine recognition, while the side-chain atoms are required for guanine recognition. Mutational analysis of the GEA motif revealed that the acquisition of GTP reactivity is accompanied by an extended activity toward inosine triphosphate (ITP) and xanthosine triphosphate (XTP). Along with the evolutionary analysis data that point to strong negative selection of the GEA motif, these results suggest that the GTP responsiveness of PI5P4Kβ has evolved from a compromised trade-off between activity and specificity, underpinning the development of the GTP-dependent stress resilience.

PubMed: 35504278
DOI: 10.1016/j.str.2022.04.004

実験手法

X-RAY DIFFRACTION (3.45 Å)