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 】

• Glycan-binding properties of SARS-CoV-2 spike proteins: interactions with aminoglycoside antibiotics.

  Hatakeyama D, Shoji M, Miki Y, Ueki S, Yamaguchi K, Nakashima K, Tanaka Y, Yokogawa M, Osawa M, Kasai Y, Imagawa H, Hashimoto R, Takayama K, Kuzuhara T

  Scientific reports  2026.03

  • Access to Document (DOI)

• 14-3-3ζ interacts with DNA-binding domain of FOXO3a and competitively dissociates DNA by dual-motif tethering

  Enomoto S., Kuwayama T., Nakatsuka S., Yokogawa M., Kawatsu K., Nakamura R., Kimura T., Tanabe M., Senda T., Saito J., Saya H., Osawa M.

  Nature Communications 17 ( 1 ) 1503 2026.02

  　View Summary

  In cancer cells, Ras protein mutations activate a signaling cascade that phosphorylates kinases, transcription, and translation factors, driving cancer cell proliferation. One such factor, FOXO3a, promotes apoptosis-related gene transcription. However, in many cancer cells, FOXO3a is phosphorylated and is bound to 14-3-3ζ at phosphorylation sites. The 14-3-3ζ binding displaces phosphorylated FOXO3a from DNA, suppressing apoptosis. Since the phosphorylation sites are far from the DNA-binding domain (DBD) of FOXO3a, the mechanism of displacement remains unclear. Using isothermal titration calorimetry and fluorescence-detection size-exclusion chromatography, we find that 14-3-3ζ strongly displaces DNA from di-phosphorylated FOXO3a (dpFOXO3a), despite similar dissociation constants for dpFOXO3a–14-3-3ζ and dpFOXO3a–DNA. Nuclear magnetic resonance data identify weak, but direct binding of 14-3-3ζ to the DBD, suggesting direct competition. These findings suggest that 14-3-3ζ enhances its competitive ability by dual tethering to the DBD of FOXO3a via phosphorylation sites, effectively displacing DNA.

  • Access to Document (DOI)

• 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)

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

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

• Structural basis for the hepatocyte specific entry and replication mechanisms of hapatitis B virus and structural based drug discovery

  Yokogawa, Mariko

  科学研究費補助金研究成果報告書 2023

• Structural mechanism of voltage-gated ion channels based on the functional structures and their transitions

  Yokogawa, Mariko

  科学研究費補助金研究成果報告書 2023

• 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

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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 】

• Structural basis for BTG2-Caf1-dependent deadenylation regulated by dynamic interactions between poly(A) and PABPC1

  Nao Kataoka, Mariko Yokogawa, Yuichiro Ishii, Erika Shiro, Hiroka Takashima, Ryoichi Sawazaki, Takeru Sagae, Koichi Ogami, Shin-ichi Hoshino, Masanori Osawa

  [Domestic presentation]  第48回日本分子生物学会年会, 

  2025.12

  , 

  Poster presentation

• 新型コロナウイルスの侵入を阻害するタンパク質タンパク質相互作用阻害化合物の創製

  横川真梨子, 金一駿希, 堀内まほろ, 大竹帝河, 米澤朋起, 清水祐吾, 池田和由, 山本雄一朗, 酒井祥太, 清水芳実, 野口耕司, 深澤征義, 伊倉光彦, 大澤匡範

  [Domestic presentation]  第64回NMR討論会, 

  2025.11

  , 

  Oral presentation (general)

• 14-3-3ζ interacts with DNA-binding domain of FOXO3a and competitively dissociates DNA by dual-motif tethering

  Shota Enomoto, Tomoya Kuwayama, Shoichi Nakatsuka, Mariko Yokogawa, Kosaku Kawatsu, Risa Nakamura, Tomomi Kimura, Mikio Tanabe, Toshiya Senda, Jun Saito, Hideyuki Saya, Masanori Osawa

  [Domestic presentation]  第64回NMR討論会, 

  2025.11

  , 

  Poster presentation

• NMR化学シフト変化に基づく低親和性リガンドの結合様式推定手法の構築

  小島行人, 石田英子, 米澤朋起, 原田彩佳, 前川こひろ, 横川真梨子, 清水祐吾, 池田和由, 大澤匡範

  [Domestic presentation]  第64回NMR討論会, 

  2025.11

  , 

  Poster presentation

• ALS関連タンパク質TDP-43の凝集と核酸による抑制機構の解明

  西村 錬, 西田 優理華, 八城 立樹, 坂上 史佳, 三浦 元輝, 横田 隆徳, 石田 英子, 横川 真梨子, 大澤 匡範

  [Domestic presentation]  第64回NMR討論会, 

  2025.11

  , 

  Poster presentation

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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