6PCL

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

Summary for 6PCL

• Entry DOI: 10.2210/pdb6pcl/pdb
• Descriptor: 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)
• Functional Keywords: inositol pyrophosphate, inositol phosphate, kinase, phosphatase, ppip5k, cell polarity, osmotic response, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 17999.20

Authors

Dollins, D.E.,Neubauer, J.,Dong, J.,York, J.D. (deposition date: 2019-06-17, release date: 2020-04-29, Last modification date: 2023-10-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.3 Å)