PDBsum entry 6pcl

Hydrolase

PDB id: 6pcl

Contents

Protein chain

135 a.a.

Ligands

I7P

Metals

_CL ×2

_MG ×3

Waters ×160

PDB id:

6pcl

Name:

Hydrolase

Title:

Crystal structure of human diphosphoinositol polyphosphate phosphohydrolase 1 in complex with 5-ip7

Structure:

Diphosphoinositol polyphosphate phosphohydrolase 1. Chain: a. Fragment: residues 1-148. Synonym: dipp-1,diadenosine 5',5'''-p1,p6-hexaphosphate hydrolase 1, nucleoside diphosphate-linked moiety x motif 3,nudix motif 3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nudt3, dipp, dipp1. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.30Å R-factor: 0.144 R-free: 0.161

Authors:

D.E.Dollins,J.Neubauer,J.Dong,J.D.York

Key ref:

D.E.Dollins et al. (2020). Vip1 is a kinase and pyrophosphatase switch that regulates inositol diphosphate signaling. Proc Natl Acad Sci U S A, 117, 9356-9364. PubMed id: 32303658 DOI: 10.1073/pnas.1908875117

Date:

17-Jun-19 Release date: 29-Apr-20

Protein chain

O95989  (NUDT3_HUMAN) -  Diphosphoinositol polyphosphate phosphohydrolase 1 from Homo sapiens

Seq: 172 a.a.

Struc: 135 a.a.

Enzyme reactions

• Enzyme class: E.C.3.6.1.52 - diphosphoinositol-polyphosphate diphosphatase.
• Reaction: diphospho-myo-inositol polyphosphate + H2O = myo-inositol polyphosphate + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1073/pnas.1908875117

Proc Natl Acad Sci U S A 117:9356-9364 (2020)

PubMed id: 32303658

Vip1 is a kinase and pyrophosphatase switch that regulates inositol diphosphate signaling.

D.E.Dollins, W.Bai, P.C.Fridy, J.C.Otto, J.L.Neubauer, S.G.Gattis, K.P.M.Mehta, J.D.York.

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-IP₇ and 1,5-IP₈ 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.