PDBsum entry 3x0c

Transferase

PDB id: 3x0c

Contents

Protein chains

319 a.a.

Ligands

5GP ×4

Waters ×42

PDB id:

3x0c

Name:

Transferase

Title:

Crystal structure of pip4kiibeta i368a complex with gmp

Structure:

Phosphatidylinositol 5-phosphate 4-kinase type-2 beta. Chain: a, b. Fragment: unp residues 31-416. Synonym: 1-phosphatidylinositol 5-phosphate 4-kinase 2-beta, diphosphoinositide kinase 2-beta, phosphatidylinositol 5-phosphate 4- kinase type ii beta, pi(5)p 4-kinase type ii beta, pip4kii-beta, ptdins(5)p-4-kinase isoform 2-beta. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pip4k2b. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.55Å R-factor: 0.225 R-free: 0.268

Authors:

K.Takeuchi,Y.H.Lo,K.Sumita,M.Senda,J.Terakawa,A.Dimitoris, J.W.Locasale,M.Sasaki,H.Yoshino,Y.Zhang,E.R.Kahoud,T.Takano, T.Yokota,B.Emerling,J.A.Asara,T.Ishida,I.Shimada,T.Daikoku, L.C.Cantley,T.Senda,A.T.Sasaki

Key ref:

K.Sumita et al. (2016). The Lipid Kinase PI5P4Kβ Is an Intracellular GTP Sensor for Metabolism and Tumorigenesis. Mol Cell, 61, 187-198. PubMed id: 26774281 DOI: 10.1016/j.molcel.2015.12.011

Date:

09-Oct-14 Release date: 14-Oct-15

Protein chains

P78356  (PI42B_HUMAN) -  Phosphatidylinositol 5-phosphate 4-kinase type-2 beta from Homo sapiens

Seq: 416 a.a.

Struc: 319 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.1.149 - 1-phosphatidylinositol-5-phosphate 4-kinase.
• Pathway: 1-Phosphatidyl-myo-inositol Metabolism
• Reaction: a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ADP + H⁺

1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + ATP = 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ADP (Bound ligand (Het Group name = 5GP) matches with 82.14% similarity) + H(+)

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

Added reference

DOI no: 10.1016/j.molcel.2015.12.011

Mol Cell 61:187-198 (2016)

PubMed id: 26774281

The Lipid Kinase PI5P4Kβ Is an Intracellular GTP Sensor for Metabolism and Tumorigenesis.

K.Sumita, Y.H.Lo, K.Takeuchi, M.Senda, S.Kofuji, Y.Ikeda, J.Terakawa, M.Sasaki, H.Yoshino, N.Majd, Y.Zheng, E.R.Kahoud, T.Yokota, B.M.Emerling, J.M.Asara, T.Ishida, J.W.Locasale, T.Daikoku, D.Anastasiou, T.Senda, A.T.Sasaki.

ABSTRACT

While cellular GTP concentration dramatically changes in response to an organism's cellular status, whether it serves as a metabolic cue for biological signaling remains elusive due to the lack of molecular identification of GTP sensors. Here we report that PI5P4Kβ, a phosphoinositide kinase that regulates PI(5)P levels, detects GTP concentration and converts them into lipid second messenger signaling. Biochemical analyses show that PI5P4Kβ preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation, and its activity reflects changes in direct proportion to the physiological GTP concentration. Structural and biological analyses reveal that the GTP-sensing activity of PI5P4Kβ is critical for metabolic adaptation and tumorigenesis. These results demonstrate that PI5P4Kβ is the missing GTP sensor and that GTP concentration functions as a metabolic cue via PI5P4Kβ. The critical role of the GTP-sensing activity of PI5P4Kβ in cancer signifies this lipid kinase as a cancer therapeutic target.