News

2022/11/10

Award Associate Professor Takumi Ueda awarded the Young Scientist Award (Shinposho) from Nuclear Magnetic Resonance Society of Japan.

Associate Professor Takumi Ueda PhD. was awarded the prise for his substential contribution to the advance of science by using NMR.

2022/10/24

Notice Prof. Kurt Wüthrich, 2002 Nobel Prize Laureate in Chemistry, gave us a lecture on "Life with NMR".

2022/7/1

Publication The Structure paper was accepted to the cover.

2022/5/3

Publication Unraveling the Trick of Human GTP Sensor Protein Evolution -Evolutionary Acquisition of PI5P4Kβ for Stress Resilience-

Structure, 2022, 30(6), P886-899.E4

  • The GEA motif that enables PI5P4Kβ to recognize GTP was identified.
  • The GEA motif binds not only ATP/GTP but also other minor energy molecules.
  • PI5P4Kβ evolved into a stress-resilient GTP sensor protein by acquiring two successive mutations in the GEA motif.
  • The retrograde mutations unraveled a way that life efficiently acquires new cellular functions

 A joint research team of the University of Tokyo, University of Cincinnati, High Energy Accelerator Research Organization (KEK), Keio University, Rikkyo University, Hoshi University, Tokai University, and Kansai Medical University unveiled a way that a GTP-sensing kinase PI5P4Kβ evolutionary acquired a function to sense GTP levels in cells and regulate energy metabolism and cell growth.
 Organisms survive by dynamically changing the concentrations of intracellular metabolites and the enzyme activity in response to the ever-changing external environments. In order for cells to be functional, it is necessary to constantly monitor the amounts of energy molecules that drive reactions within the cell and control reactions that consume energy molecules.
 We have focused on GTP, which is the second most abundant energy molecule in the cell and has unique functions distinct from ATP. We have been studying how the intracellular concentration of GTP is monitored and how energy metabolism in cells is regulated according to GTP concentrations. In the course of such studies, we discovered in 2016 that phosphatidylinositol 5-phosphate 4-kinase β (PI5P4Kβ) uses GTP as a physiological phosphate donor, unlike many other kinases, and regulates cell proliferation under stress in response to GTP. The emergence of PI5P4Kβ roughly coincided with the emergence of vertebrates. Therefore, it can be assumed that a new energy metabolism system responsive to GTP concentrations was acquired in organisms that are higher than vertebrates. However, how the GTP sensor function of PI5P4Kβ was acquired has remained unclear.
 This paper shows that PI5P4Kβ became a GTP-sensing kinase by acquiring a short sequence named the GEA (Guanine Efficient-Association) motif. By comparing PI5P4Kβ-nucleotide complex structures with those of 660 kinases and 128 G proteins, we found that the ATP-binding mode of the GEA motif is similar to that of other kinases, while its side chains and water molecules play an important role in the recognition of GTP (see the top of the figure ). Furthermore, the introduction of the retrograde mutations that make the GEA motif (right in the figure) back into its ancestral sequence (left in the figure) revealed that the acquisition of the GTP sensing function is accompanied by an expansion of activity toward other minor energy molecules such as ITP and XTP (bottom right in the figure). The result suggests that the GTP-sensing activity of PI5P4Kβ was acquired as a trade-off for the kinase's ATP specificity in the ultimate choice between activity and specificity. In the intermediate mutation (center of the figure), the original ATP-dependent activity was maintained. This can be considered as an example of how an organism can efficiently search for new cellular functions by random trial and error while minimizing the adverse effects of losing the original functions.
 The paper was published online in Structure on May 2, 2022 at 11:00 AM EST. A print version will be published on July 7, 2022.

Figure: Recognition of ATP and GTP by GEA motifs and their evolutionary acquisition.
(Reproduced with some modifications from Takeuchi, Ikeda, Senda et al., Structure, 2022)

2022/5/2

Notice The 4th Workshop on NMR from the Basics - NMR in Drug Discovery and Industrial Research -

Dates: Thursday, May 19 ~ Friday, May 20, 2022
Online seminar via Zoom
No registration fee required

In drug discovery, a comprehensive evaluation of the structures, interactions, and dynamics of drug molecules and their target biomolecules is necessary. In such situations, nuclear magnetic resonance (NMR), which provides multifaceted information about molecules in solution, is used as an effective drug discovery research tool. In addition to drug discovery, NMR can also provide useful information in various situations, especially when various physical properties are present, such as in the study of foods and chemical products. This workshop will focus on NMR and structural analysis techniques in drug discovery and industrial research. Active researchers from academia and industry will give lectures aiming to exchange information between industrial and academic research.

Program:
May 19
Chair: Tomohide Saio

TimeTitlePresenter
13:00~13:50Review of the previous seminar, introduction, and basic lectureProf. Koh Takeuchi [Graduate school of Pharmaceutical Sciences, The University of Tokyo]
13:50~14:35Lecture 1-1 Food R&D and NMRDr. Hideyuki Yamaguchi [Research Institute for Bioscience Products & Fine Chemicals, Ajinomoto Co.]
Break
14:45~15:30Lecture 1-2 Molecular recognition of cell surface receptors and drug discoveryDr. Katsumi Maenaka [Graduate school of Pharmaceutical Sciences, Hokkaido University]
15:30~16:15Lecture 1-3 My thoughts through 17 years of NMR activities in drug discovery (tentative)Dr. Takuya Torizawa [Chugai Pharmaceutical Co.]
19:00~Online Reception

5/20
Chair: Tomohide Saio

TimeTitlePresenter
9:30~10:15Lecture 2-1 Interaction analysis between RNA and small molecule compounds by NMR for drug discoveryDr. Gota Kawai [Chiba Institute of Advanced Industrial Science and Technology].
10:15~11:15Special Lecture 2-2Prof. Haribabu Arthanari [Harvard Medical School].
11:15~11:30ReviewYohei Miyanoiri

Organized by: Institute for Protein Research, Osaka University
Sponsored by: Next Generation NMR Working Group, The Biophysical Society of Japan
Sponsors: Tomohide Saio, Koh Takeuchi, Yohei Miyanoiri, Hiromasa Yagi

Pre-registration and more information: https://nextnmr.jp

2022/3/28

Notice The new webpage of the Laboratory of Physical Chemistry was launched.

2022/3/1

Notice Defense presentation for the doctoral thesis of Mr. Tomoki Yokomizo, and those for master thesis of Ms. Aya Aoki and Mr. Katumune Donai were successfully conducted. Everyone conveyed fanatic presentations.

2021/10/1

Notice The Laboratory of Physical Chemistry has started with the new administration.