5W7T

STRUCTURE OF PHOSPHORYLATED WNK1

5W7T の概要

• エントリーDOI: 10.2210/pdb5w7t/pdb
• 分子名称: Serine/threonine-protein kinase WNK1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (3 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Rattus norvegicus (Rat)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64740.03

構造登録者

JIOU, J.,CHLEBOWICZ, J.,AKELLA, R.,GOLDSMITH, E.J. (登録日: 2017-06-20, 公開日: 2018-06-20, 最終更新日: 2025-08-06)

主引用文献

Akella, R.,Drozdz, M.A.,Humphreys, J.M.,Jiou, J.,Durbacz, M.Z.,Mohammed, Z.J.,He, H.,Liwocha, J.,Sekulski, K.,Goldsmith, E.J.
A Phosphorylated Intermediate in the Activation of WNK Kinases.
Biochemistry, 59:1747-1755, 2020

PubMed Abstract: WNK kinases autoactivate by autophosphorylation. Crystallography of the kinase domain of WNK1 phosphorylated on the primary activating site (pWNK1) in the presence of AMP-PNP reveals a well-ordered but inactive configuration. This new pWNK1 structure features specific and unique interactions of the phosphoserine, less hydration, and smaller cavities compared with those of unphosphorylated WNK1 (uWNK1). Because WNKs are activated by osmotic stress in cells, we addressed whether the structure was influenced directly by osmotic pressure. pWNK1 crystals formed in PEG3350 were soaked in the osmolyte sucrose. Suc-WNK1 crystals maintained X-ray diffraction, but the lattice constants and pWNK1 structure changed. Differences were found in the activation loop and helix C, common switch loci in kinase activation. On the basis of these structural changes, we tested for effects on activity of two WNKs, pWNK1 and pWNK3. The osmolyte PEG400 enhanced ATPase activity. Our data suggest multistage activation of WNKs.

PubMed: 32314908
DOI: 10.1021/acs.biochem.0c00146

実験手法

X-RAY DIFFRACTION (2.01 Å)