3x02

Crystal structure of PIP4KIIBETA complex with GMP

spinqualitylabelsall models 3x02, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3x02 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 5GP Related: 3wzz, 3x01, 3x03, 3x04, 3x05, 3x06, 3x07, 3x08, 3x09, 3x0a, 3x0b, 3x0c Gene: PIP4K2B (HUMAN) Activity: 1-phosphatidylinositol-5-phosphate 4-kinase, with EC number 2.7.1.149 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PI42B_HUMAN] Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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