5DGH

Crystal structure of the catalytic domain of human diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) in complex with AMP-PNP and 5-(PCP)-IP5

5DGH の概要

• エントリーDOI: 10.2210/pdb5dgh/pdb
• 関連するPDBエントリー: 5DGI
• 分子名称: Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, Methylenebisphosphonate inositol pentakisphosphate, ... (7 entities in total)
• 機能のキーワード: transferase inositol diphosphoinositol pentakisphosphate kinase analog methylenebisphosphonate ppip5k atp-grasp pyrophosphate diphosphate, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39425.15

構造登録者

Wang, H.,Shears, S.B. (登録日: 2015-08-27, 公開日: 2016-08-10, 最終更新日: 2023-09-27)

主引用文献

Hager, A.,Wu, M.,Wang, H.,Brown, N.W.,Shears, S.B.,Veiga, N.,Fiedler, D.
Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.
Chemistry, 22:12406-12414, 2016

PubMed Abstract: The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions.

PubMed: 27460418
DOI: 10.1002/chem.201601754

実験手法

X-RAY DIFFRACTION (2.1 Å)