6PCL

Crystal structure of human diphosphoinositol polyphosphate phosphohydrolase 1 in complex with 5-IP7

6PCL の概要

• エントリーDOI: 10.2210/pdb6pcl/pdb
• 分子名称: Diphosphoinositol polyphosphate phosphohydrolase 1, (1r,2R,3S,4s,5R,6S)-2,3,4,5,6-pentakis(phosphonooxy)cyclohexyl trihydrogen diphosphate, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: inositol pyrophosphate, inositol phosphate, kinase, phosphatase, ppip5k, cell polarity, osmotic response, hydrolase
• 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: 17999.20

構造登録者

Dollins, D.E.,Neubauer, J.,Dong, J.,York, J.D. (登録日: 2019-06-17, 公開日: 2020-04-29, 最終更新日: 2023-10-11)

主引用文献

Dollins, D.E.,Bai, W.,Fridy, P.C.,Otto, J.C.,Neubauer, J.L.,Gattis, S.G.,Mehta, K.P.M.,York, J.D.
Vip1 is a kinase and pyrophosphatase switch that regulates inositol diphosphate signaling.
Proc.Natl.Acad.Sci.USA, 117:9356-9364, 2020

PubMed Abstract: Inositol diphosphates (PP-IPs), also known as inositol pyrophosphates, are high-energy cellular signaling codes involved in nutrient and regulatory responses. We report that the evolutionarily conserved gene product, Vip1, possesses autonomous kinase and pyrophosphatase domains capable of synthesis and destruction of D-1 PP-IPs. Our studies provide atomic-resolution structures of the PP-IP products and unequivocally define that the Vip1 gene product is a highly selective 1-kinase and 1-pyrophosphatase enzyme whose activities arise through distinct active sites. Kinetic analyses of kinase and pyrophosphatase parameters are consistent with Vip1 evolving to modulate levels of 1-IP and 1,5-IP Individual perturbations in kinase and pyrophosphatase activities in cells result in differential effects on vacuolar morphology and osmotic responses. Analogous to the dual-functional key energy metabolism regulator, phosphofructokinase 2, Vip1 is a kinase and pyrophosphatase switch whose 1-PP-IP products play an important role in a cellular adaptation.

PubMed: 32303658
DOI: 10.1073/pnas.1908875117

実験手法

X-RAY DIFFRACTION (1.3 Å)