3x0c

Crystal structure of PIP4KIIBETA I368A complex with GMPCrystal structure of PIP4KIIBETA I368A complex with GMP

Structural highlights

3x0c is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.55Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PI42B_HUMAN Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.^[1]

Publication Abstract from PubMed

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 PI5P4Kbeta, a phosphoinositide kinase that regulates PI(5)P levels, detects GTP concentration and converts them into lipid second messenger signaling. Biochemical analyses show that PI5P4Kbeta 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 PI5P4Kbeta is critical for metabolic adaptation and tumorigenesis. These results demonstrate that PI5P4Kbeta is the missing GTP sensor and that GTP concentration functions as a metabolic cue via PI5P4Kbeta. The critical role of the GTP-sensing activity of PI5P4Kbeta in cancer signifies this lipid kinase as a cancer therapeutic target.

The Lipid Kinase PI5P4Kbeta Is an Intracellular GTP Sensor for Metabolism and Tumorigenesis.,Sumita K, Lo YH, Takeuchi K, Senda M, Kofuji S, Ikeda Y, Terakawa J, Sasaki M, Yoshino H, Majd N, Zheng Y, Kahoud ER, Yokota T, Emerling BM, Asara JM, Ishida T, Locasale JW, Daikoku T, Anastasiou D, Senda T, Sasaki AT Mol Cell. 2016 Jan 21;61(2):187-98. doi: 10.1016/j.molcel.2015.12.011. Epub 2016 , Jan 7. PMID:26774281^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Castellino AM, Parker GJ, Boronenkov IV, Anderson RA, Chao MV. A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase. J Biol Chem. 1997 Feb 28;272(9):5861-70. PMID:9038203
↑ Sumita K, Lo YH, Takeuchi K, Senda M, Kofuji S, Ikeda Y, Terakawa J, Sasaki M, Yoshino H, Majd N, Zheng Y, Kahoud ER, Yokota T, Emerling BM, Asara JM, Ishida T, Locasale JW, Daikoku T, Anastasiou D, Senda T, Sasaki AT. The Lipid Kinase PI5P4Kbeta Is an Intracellular GTP Sensor for Metabolism and Tumorigenesis. Mol Cell. 2016 Jan 21;61(2):187-98. doi: 10.1016/j.molcel.2015.12.011. Epub 2016 , Jan 7. PMID:26774281 doi:http://dx.doi.org/10.1016/j.molcel.2015.12.011

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OCA

[1] Castellino AM, Parker GJ, Boronenkov IV, Anderson RA, Chao MV. A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase. J Biol Chem. 1997 Feb 28;272(9):5861-70. PMID:9038203

[2] Sumita K, Lo YH, Takeuchi K, Senda M, Kofuji S, Ikeda Y, Terakawa J, Sasaki M, Yoshino H, Majd N, Zheng Y, Kahoud ER, Yokota T, Emerling BM, Asara JM, Ishida T, Locasale JW, Daikoku T, Anastasiou D, Senda T, Sasaki AT. The Lipid Kinase PI5P4Kbeta Is an Intracellular GTP Sensor for Metabolism and Tumorigenesis. Mol Cell. 2016 Jan 21;61(2):187-98. doi: 10.1016/j.molcel.2015.12.011. Epub 2016 , Jan 7. PMID:26774281 doi:http://dx.doi.org/10.1016/j.molcel.2015.12.011

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