KEIO RESEARCHERS INFORMATION SYSTEM

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 博士（薬学）, The University of Tokyo, Coursework

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• 薬剤師免許

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Pharmaceutical analytical chemistry and physicochemistry

• Life Science / Structural biochemistry

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• NMR

• イオンチャネル

• ウイルス感染症

• 構造生物学

• 翻訳因子

Books 【 Display / hide 】

Books 【 Display / hide 】

• Peptide Toxins Targeting KV Channels

  Matsumura K., Yokogawa M., Osawa M., Handbook of Experimental Pharmacology, 2021

  　View Summary

  A number of peptide toxins isolated from animals target potassium ion (K+) channels. Many of them are particularly known to inhibit voltage-gated K+ (KV) channels and are mainly classified into pore-blocking toxins or gating-modifier toxins. Pore-blocking toxins directly bind to the ion permeation pores of KV channels, thereby physically occluding them. In contrast, gating-modifier toxins bind to the voltage-sensor domains of KV channels, modulating their voltage-dependent conformational changes. These peptide toxins are useful molecular tools in revealing the structure-function relationship of KV channels and have potential for novel treatments for diseases related to KV channels. This review focuses on the inhibition mechanism of pore-blocking and gating-modifier toxins that target KV channels.

• Nuclear magnetic resonance approaches for characterizing protein-protein interactions

  Toyama Y., Mase Y., Kano H., Yokogawa M., Osawa M., Shimada I., Methods in Molecular Biology, 2018

  　View Summary

  The gating of potassium ion (K+) channels is regulated by various kinds of protein-protein interactions (PPIs). Structural investigations of these PPIs provide useful information not only for understanding the gating mechanisms of K+ channels, but also for developing the pharmaceutical compounds targeting K+ channels. Here, we describe a nuclear magnetic resonance spectroscopic method, termed the cross saturation (CS) method, to accurately determine the binding surfaces of protein complexes, and its application to the investigation of the interaction between a G protein-coupled inwardly rectifying K+ channel and a G protein α subunit.

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• NMR ¹H, ¹³C, ¹⁵N backbone resonance assignments of 14-3-3ζ binding region of human FOXO3a (residues 1-284)

  Enomoto S., Nakatsuka S., Kuwayama T., Kawatsu K., Yokogawa M., Osawa M.

  Biomolecular NMR Assignments 18 ( 2 ) 275 - 283 2024.12

  Research paper (scientific journal), Accepted,  ISSN  18742718

  　View Summary

  In tumors, mutation in Ras proteins stimulates a signaling cascade through phosphorylation. Downstream of the cascade, many transcription and translation factors are up- or down-regulated by phosphorylation, leading to cancer progression. This phosphorylation cascade is sustained by 14-3-3ζ protein. 14-3-3ζ binds to its client proteins that are Ser/Thr-phosphorylated and prevents their dephosphorylation. One of those transcription factors is FOXO3a, whose transcriptional activity is suppressed in the phosphorylation cascade. FOXO3a binds to specific DNA sequences and activates the transcription of apoptosis-related proteins. In cancer cells, however, FOXO3a is phosphorylated, bound to 14-3-3ζ, and dissociated from the DNA, resulting in FOXO3a inactivation. To elucidate the mechanism of FOXO3a inactivation by the 14-3-3ζ binding, we aim to perform NMR analysis of the interaction between 14-3-3ζ and di-phosphorylated FOXO3a residues 1-284 (dpFOXO3a). Here, we report the backbone resonance assignments of dpFOXO3a, which are transferred from those of the N-terminal domain (NTD) and the DNA-binding domain (DBD) of dpFOXO3a.

  • Access to Document (DOI)

• Ribonuclease inhibitor and angiogenin system regulates cell type–specific global translation

  Stillinovic M., Sarangdhar M.A., Andina N., Tardivel A., Greub F., Bombaci G., Ansermet C., Zatti M., Saha D., Xiong J., Sagae T., Yokogawa M., Osawa M., Heller M., Keogh A., Keller I., Angelillo-Scherrer A., Allam R.

  Science Advances (Science Advances)  10 ( 22 ) eadl0320 2024.05

  Research paper (scientific journal), Accepted

  　View Summary

  Translation of mRNAs is a fundamental process that occurs in all cell types of multicellular organisms. Conventionally, it has been considered a default step in gene expression, lacking specific regulation. However, recent studies have documented that certain mRNAs exhibit cell type–specific translation. Despite this, it remains unclear whether global translation is controlled in a cell type–specific manner. By using human cell lines and mouse models, we found that deletion of the ribosome-associated protein ribonuclease inhibitor 1 (RNH1) decreases global translation selectively in hematopoietic-origin cells but not in the non–hematopoietic-origin cells. RNH1-mediated cell type–specific translation is mechanistically linked to angiogenin-induced ribosomal biogenesis. Collectively, this study unravels the existence of cell type–specific global translation regulators and highlights the complex translation regulation in vertebrates.

  • Access to Document (DOI)

• Applying deep learning to iterative screening of medium-sized molecules for protein-protein interaction-targeted drug discovery

  Shimizu Y., Yonezawa T., Bao Y., Sakamoto J., Yokogawa M., Furuya T., Osawa M., Ikeda K.

  Chemical Communications (Chemical Communications)  59 ( 44 ) 6722 - 6725 2023.05

  Research paper (scientific journal), Accepted,  ISSN  13597345

  　View Summary

  We combined a library of medium-sized molecules with iterative screening using multiple machine learning algorithms that were ligand-based, which resulted in a large increase of the hit rate against a protein-protein interaction target. This was demonstrated by inhibition assays using a PPI target, Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2), and a deep neural network model based on the first-round assay data showed a highest hit rate of 27.3%. Using the models, we identified novel active and non-flat compounds far from public datasets, expanding the chemical space.

  • Access to Document (DOI)

• TDP-43 N-terminal domain dimerisation or spatial separation by RNA binding decreases its propensity to aggregate

  Miura M., Sakaue F., Matsuno H., Morita K., Yoshida A., Hara R.I., Nishimura R., Nishida Y., Yokogawa M., Osawa M., Yokota T.

  FEBS Letters (FEBS Letters)  597 ( 12 ) 1667 - 1676 2023

  Research paper (scientific journal), Accepted,  ISSN  00145793

  　View Summary

  Aggregation of the 43 kDa TAR DNA-binding protein (TDP-43) is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). RNA binding and TDP-43 N-terminal domain dimerisation has been suggested to ameliorate TDP-43 aggregation. However, the relationship between these factors and the solubility of TDP-43 is largely unknown. Therefore, we developed new oligonucleotides that can recruit two TDP-43 molecules and interfere with their intermolecular interactions via spatial separation. Using these oligonucleotides and TDP-43-preferable UG-repeats, we uncovered two distinct mechanisms for modulating TDP-43 solubility by RNA binding: One is N-terminal domain dimerisation, and the other is the spatial separation of two TDP-43 molecules. This study provides new molecular insights into the regulation of TDP-43 solubility.

  • Access to Document (DOI)

• Paip2A inhibits translation by competitively binding to the RNA recognition motifs of PABPC1 and promoting its dissociation from the poly(A) tail.

  Sagae T, Yokogawa M, Sawazaki R, Ishii Y, Hosoda N, Hoshino SI, Imai S, Shimada I, Osawa M

  The Journal of biological chemistry (Journal of Biological Chemistry)  298 ( 5 ) 101844 2022.03

  Research paper (scientific journal), Accepted,  ISSN  0021-9258

  　View Summary

  Eukaryotic mRNAs possess a poly(A) tail at their 30-end, to which poly(A)-binding protein C1 (PABPC1) binds and recruits other proteins that regulate translation. Enhanced poly(A)dependent translation, which is also PABPC1 dependent, promotes cellular and viral proliferation. PABP-interacting protein 2A (Paip2A) effectively represses poly(A)-dependent translation by causing the dissociation of PABPC1 from the poly(A) tail; however, the underlying mechanism remains unknown. This study was conducted to investigate the functional mechanisms of Paip2A action by characterizing the PABPC1–poly(A) and PABPC1–Paip2A interactions. Isothermal titration calorimetry and NMR analyses indicated that both interactions predominantly occurred at the RNA recognition motif (RRM) 2–RRM3 regions of PABPC1, which have comparable affinities for poly(A) and Paip2A (dissociation constant, Kd = 1 nM). However, the Kd values of isolated RRM2 were 200 and 4 μM in their interactions with poly(A) and Paip2A, respectively; Kd values of 5 and 1 μM were observed for the interactions of isolated RRM3 with poly(A) and Paip2A, respectively. NMR analyses also revealed that Paip2A can bind to the poly(A)binding interfaces of the RRM2 and RRM3 regions of PABPC1. Based on these results, we propose the following functional mechanism for Paip2A: Paip2A initially binds to the RRM2 region of poly(A)-bound PABPC1, and RRM2-anchored Paip2A effectively displaces the RRM3 region from poly(A), resulting in dissociation of the whole PABPC1 molecule. Together, our findings provide insight into the translation repression effect of Paip2A and may aid in the development of novel anticancer and/or antiviral drugs.

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• Structural basis for PIP2 recognition, embedded in membranes, by PIP2-binding proteins

  Yokogawa, Mariko

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2022

• Structural basis for PIP2 recognition, embedded in membranes, by PIP2-binding proteins

  Yokogawa, Mariko

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2021

• Structural analysis of hepatocyte specific entry and replication mechanism of hepatitis B virus

  Yokogawa, Mariko

  科学研究費補助金研究成果報告書 2020

• Structural basis for the hepatocyte-specific entry of hepatitis B virus

  Yokogawa, Mariko

  福澤諭吉記念慶應義塾学事振興基金事業報告集 (福澤基金運営委員会)  2020

• Functional regulation of voltage-gated ion channels targeting the voltage sensor

  Yokogawa, Mariko

  科学研究費補助金研究成果報告書 2019

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Nuclear Magnetic Resonance Approaches for Characterizing Protein-Protein Interactions.

  Toyama Y, Mase Y, Kano H, Yokogawa Mariko, Osawa M, Shimada I

  Methods Mol Biol. 1684   115 - 128 2018.10

  Article, review, commentary, editorial, etc. (scientific journal), Joint Work

  • Access to Document (DOI)

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• Discovery of COVID-19 therapeutic seeds using angiotensin-converting enzyme 2 (ACE2) immobilized beads

  江川 奏, 齋藤 駿, 山本 瑞生, 横川 真梨子, 大澤 匡範, 荻 貴之, 荒井 緑

  日本薬学会第145年会, 

  2025.03

• Angiotensin-converting enzyme 2 (ACE2) 担持ビーズを用いた 新型コロナウイルス感染症治療薬シードの探索

  江川 奏, 齋藤 駿, 山本 瑞生, 横川 真梨子, 大澤 匡範, 荻 貴之, 荒井 緑

  第10回 食品薬学シンポジウム, 

  2024.10

  , 

  Poster presentation

• Development of novel anti-HBV drugs based on AI technology using bile acid derivatives to inhibit HBV and NTCP binding

  Okumura A, Ikeda K, Arai J , Muraki Y , Nishimura S, Inden N, Yokogawa M, Yamashita Y, Iguchi Y, Ohashi H, Watashi K, Wakita T, Une M, Osawa M, Ito K

  International HBV Meeting 2024, 

  2024.09

  , 

  Poster presentation

• 新規Keap1-Nrf2タンパク質間相互作用阻害剤とKeap1結合の構造基盤

  小島 行人, 石田 英子, 原田 彩佳, 米澤 朋起, 清水 祐吾, 池田 和由, 横川 真梨子, 大澤 匡範

  第21回次世代を担う若手のためのフィジカル・ファーマフォーラム (PPF2024) (レクトーレ葉山　湘南国際村) , 

  2024.08

  , 

  Oral presentation (general), 日本薬学会　物理系薬学部会

• BTG2によるCaf1依存的ポリA分解の促進機構の解明

  片岡 奈緒, 横川 真梨子, 石井 裕一郎, 城 えりか, 高嶋 大翔, 沢崎 綾一, 寒河江 彪流, 尾上 耕一, 星野 真一, 大澤 匡範

  第21回次世代を担う若手のためのフィジカル・ファーマフォーラム (PPF2024)) (レクトーレ葉山　湘南国際村) , 

  2024.08

  , 

  Oral presentation (general), 日本薬学会　物理系薬学部会

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

Research Projects of Competitive Funds, etc. 【 Display / hide 】

• B型肝炎ウイルスの肝細胞侵入・増殖機構の構造基盤と立体構造に基づく創薬

  2021.04

  -

  2024.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

• B型肝炎ウイルスの肝細胞侵入および増殖機構の構造生物学的解析

  2018.04

  -

  2021.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

• Structural basis for hepatitis B virus infection

  2016.04

  -

  2018.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Principal investigator

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• STUDY OF MAJOR FIELD:(PHYSICS FOR LIFE FUNCTIONS)SPRING

  2025

• STUDY OF MAJOR FIELD:(PHYSICS FOR LIFE FUNCTIONS)AUTUMN

  2025

• STUDY OF MAJOR FIELD:(PHYSICS FOR LIFE FUNCTIONS)

  2025

• SEMINAR:(PHYSICS FOR LIFE FUNCTIONS)SPRING

  2025

• SEMINAR:(PHYSICS FOR LIFE FUNCTIONS)AUTUMN

  2025

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Courses Previously Taught 【 Display / hide 】

Courses Previously Taught 【 Display / hide 】

• 薬学基礎実習

  Keio University

  2015.04

  -

  2016.03

  , 

  Autumn Semester, Laboratory work/practical work/exercise

• C1(4)物質の変化

  Keio University

  2015.04

  -

  2016.03

  , 

  Autumn Semester, Lecture

  反応速度

• 薬学実習IIA（化学、物理）

  Keio University

  2015.04

  -

  2016.03

  , 

  Spring Semester, Laboratory work/practical work/exercise