6E7F

Crystal Structure of Human Inositol Polyphosphate Multikinase (IPMK) Catalytic Core Domain

「6C8A」から置き換えられました

6E7F の概要

• エントリーDOI: 10.2210/pdb6e7f/pdb
• 分子名称: Inositol polyphosphate multikinase, SULFATE ION (3 entities in total)
• 機能のキーワード: kinase, inositol phosphate, ipmk, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64020.38

構造登録者

Blind, R.,Seacrist, C. (登録日: 2018-07-26, 公開日: 2018-11-07, 最終更新日: 2023-10-11)

主引用文献

Seacrist, C.D.,Blind, R.D.
Crystallographic and kinetic analyses of human IPMK reveal disordered domains modulate ATP binding and kinase activity.
Sci Rep, 8:16672-16672, 2018

PubMed Abstract: Inositol polyphosphate multikinase (IPMK) is a member of the IPK-superfamily of kinases, catalyzing phosphorylation of several soluble inositols and the signaling phospholipid PI(4,5)P (PIP). IPMK also has critical non-catalytic roles in p53, mTOR/Raptor, TRAF6 and AMPK signaling mediated partly by two disordered domains. Although IPMK non-catalytic functions are well established, it is less clear if the disordered domains are important for IPMK kinase activity or ATP binding. Here, kinetic and structural analyses of an engineered human IPMK lacking all disordered domains (ΔIPMK) are presented. Although the K for PIP is identical between ΔIPMK and wild type, ΔIPMK has a 1.8-fold increase in k for PIP, indicating the native IPMK disordered domains decrease IPMK activity in vitro. The 2.5 Å crystal structure of ΔIPMK is reported, confirming the conserved ATP-grasp fold. A comparison with other IPK-superfamily structures revealed a putative "ATP-clamp" in the disordered N-terminus, we predicted would stabilize ATP binding. Consistent with this observation, removal of the ATP clamp sequence increases the K for ATP 4.9-fold, indicating the N-terminus enhances ATP binding to IPMK. Together, these structural and kinetic studies suggest in addition to mediating protein-protein interactions, the disordered domains of IPMK impart modulatory capacity to IPMK kinase activity through multiple kinetic mechanisms.

PubMed: 30420721
DOI: 10.1038/s41598-018-34941-3

実験手法

X-RAY DIFFRACTION (2.5 Å)