東北大学　学際科学フロンティア研究所　奥村研究室

Koki Suzuki, Ryoya Nojiri, Motonori Matsusaki, Takuya Mabuchi, Shingo kanemura, Kotone Ishii, Hiroyuki Kumeta, Masaki Okumura,* Tomohide Saio,*  and Takahiro Muraoka.*  Redox-active chemical chaperones exhibiting promiscuous binding promote oxidative protein folding under condensed sub-millimolar conditions. Chemical Science 2024, Advance Article

Kuramochi T,# Yamashita Y,# Arai K, Kanemura S, Muraoka T,* and Okumura M.*  Boosting the enzymatic activity of CxxC motif-containing PDI family members. Chemical Communications (Camb).  2024 60, DOI: 10.1039/D4CC01712A　★Inside back coverに選出されました

Muraoka T,* Okumura M,* Saio T.* Enzymatic and synthetic regulation of polypeptide folding.Chemical Science 2024 26;15(7):2282-2299. 

Arai K.#*, Okumura M.#, Lee Y.H.#, Katayama H., Mizutani K., Lin Y., Park S.Y., Sawada K., Toyoda M., Hojo H., Inaba K., and Iwaoka M. Communications Chemistry. 2023. 6. 1-10

Okada, S., Matsumoto, Y., Takahashi R., Arai, K., Kanemura, S., Okumura M.*, and Muraoka, T.*. Semi-enzymatic acceleration of oxidative protein folding by N-methylated heteroaromatic thiols. Chemical Science. 2023, 10.1039/d3sc01540h.

Okada, S., Matsumoto, Y., Okumura, M., and Muraoka, T.*. Oxidative Protein Folding Promotion by Imidazoyl-Conjugated Thiol. Chem. Lett. 2023. 52. 202–205

Nishino, H., Kitamura, M., Okada, S., Miyake, R., Okumura, M., and Muraoka, T.*. Cysteine-based protein folding modulators for trapping intermediates and misfolded forms. RSC Adv. 2022, 12, 26658–26664

Muraoka, T.,* Saio, T., and Okumura, M. Biophysical elucidation of neural network and chemical regeneration of neural tissue. Biophys.Physicobiol. 2022. 19, e190024

Okumura, M.,* Kanemura, S.,# Matsusaki, M.,# Kinoshita, M.,# Saio, T., Ito, D., Hirayama, C., Kumeta, H., Watabe, M., Amagai, Y., Lee, Y.H., Akiyama, S., and Inaba, K.*. A unique leucine-valine adhesive motif supports structure and function of protein disulfide isomerase P5 via dimerization. Structure. 2021. 29. 1-14

Matsusaki, M., Okada, R., Tanikawa, Y., Kanemura, S., Ito, D., Lin, Y., Watabe, M., Yamaguchi, H., Saio, T., Lee, YH., Inaba, K., and Okumura, M.*. Functional Interplay Between P5 And PDI/ERp72 To Drive Protein Folding.Biology. 2021. 10. 11. 1112

Okumura, M., Noi, K., and Inaba, K*. Visualization of structural dynamics of protein disulfide isomerase enzymes in catalysis of oxidative folding and reductive unfolding. Current Opinion in Structural Biology. 2021. 66. 49-57

Tanikawa, Y.,# Kanemura, S.,# Ito, D., Lin, Y., Matsusaki, M., Kuroki, K., Yamaguchi, H., Maenaka, K., Lee, Y.H., Inaba, K., and Okumura, M.*. Ca2+ regulates ERp57-calnexin complex formation. molecules. 2021. 26. 2853

Okada, S., Matsusaki, M., Okumura, M.,* and Muraoka, T.*. Conjugate of Thiol and Guanidyl Units with Oligoethylene Glycol Linkage for Manipulation of Oxidative Protein Folding. molecules. 2021. 26. 4. 879-879

Hirayama, C., Machida, K., Noi, K., Murakawa, T., Okumura, M., Ogura, T., Imataka, H., and Inaba, K*. Distinct roles and actions of protein disulfide isomerase family enzymes in catalysis of co-translational disulfide bond formation. iScience. 2021. 4. 102296

Matsusaki, M.,# Kanemura, S.,# Kinoshita, M.,# Lee, Y.H., Inaba, K.,* and Okumura, M.*. The Protein Disulfide Isomerase family: from Proteostasis to Pathogenesis. Biochim Biophys Acta-general subjects. 2020. 1864. 129338

Kanemura, S.,# Matsusaki, M.,# Inaba, K., and Okumura, M.*. PDI Family Members as Guides for Client Folding and Assembly. Int. J. Mol. Sci. 2020. 21. E9351

Ninagawa, S.,* Tada, S.,# Okumura, M.,# Inoguchi, K.,# Kinoshita, M., Kanemura, S., Imami, K., Umezawa, H., Ishikawa, T., Okada, T., Mackin, R., Torii, S., Ishihama, Y., Inaba, K., Anazawa, T., Nagamine, T., and Mori, K*. Antipsychotic olanzapine-induced misfolding of proinsulin in the ER accounts for atypical development of diabetes. eLife. 2020. 9. e60970

Saio, T.*, Okumura, M., and Lee, Y.H*. Solution NMR for investigation of liquid-liquid phase separation. Journal of the Korean Magnetic Resonance Society 2020. 24. 2. 47-52

Okumura, M.,*# Noi, K.,# Kanemura, S., Kinoshita, M., Saio, T., Inoue, Y., Hikima, T., Akiyama, S., Ogura, T.,* and Inaba, K.*. Dynamic assembly of protein disulfide isomerase in catalysis of oxidative protein folding. Nature Chemical Biology. 2019. 15. 5. 499-509 ★Faculty of 1000に選出

Okada, S.,# Matsusaki, M.,# Arai, K., Hidaka, Y., Inaba, K., Okumura, M.,* and Muraoka, T.*. Coupling effects of thiol and urea-type groups for promotion of oxidative protein folding. Chem Commun (Camb). 2019. 55. 759-762 ★雑誌のバックカバー

Lin, Y., Sahoo, B.R., Ozawa, D., Kinoshita, M., Kang, J., Lim, M.H., Okumura, M., Huh, Y.H., Moon, E., Jang, J.H., Lee, H.J., Ryu, K.Y., Ham, S., Won, H.S., Ryu KS, Sugiki, T., Bang, J.K., Hoe, H.S., Fujiwara, T., Ramamoorthy, A., and Lee, Y.H.*. Diverse Structural Conversion and Aggregation Pathways of Alzheimer’s Amyloid-β (1-40). ACS nano. 2019. 13. 8. 8766-8783

O’Brien, H., Kanemura, S., Okumura, M., Baskin, R.P., Bandyopadhyay, P.K., Olivera, B.M., Ellgaard, L., Inaba, K., and Safavi-Hemami, H.*. Ero1-mediated reoxidation of PDI accelerates the folding of cone-snail toxins. Int. J. Mol. Sci. 2018. 11. E3418

Terakawa, M.S., Lin, Y., Kinoshita, M., Kanemura, S., Itoh, D., Sugiki, T., Okumura, M., Ramamoorthy, A., and Lee, Y.H.*. Impact of membrane curvature on amyloid aggregation. Biochim Biophys Acta Biomembr. 2018. 1860. 1741-1764

Kinoshita, M., Lin, Y., Itoh, D., Okumura, M., Markova, N., Ladbury, J.E., Sterpone, F., and Lee, Y.H.*. Energy landscape of polymorphic amyloid generation of β2-microglobulin revealed by calorimetry. Chem Commun (Camb). 2018. 57. 7995-7998

Arai, K., Takei, T., Shinozaki, R., Noguchi, N., Fujisawa, S., Katayama, H., Moroder, L., Ando, S., Okumura, M., Inaba, K., Hojo, H., and Iwaoka, M *. Characterization and optimization of two-chain folding pathways of insulin via native chain assembly. Communications Chemistry. 2018. 1. e26

Maegawa, K.I., Watanabe, S.,# Noi, K.,# Okumura, M.,# Amagai, Y.,# Inoue, M., Ushioda, R., Nagata, K., Ogura, T., and Inaba, K.*. The Highly Dynamic Nature of ERdj5 Is Key to Efficient Elimination of Aberrant Protein Oligomers through ER-Associated Degradation. Structure. 2017. 25. 6. 846-+

Arai, K.,# Takei, T.,# Okumura, M.,# Watanabe, S.,# Amagai, Y., Asahina, Y., Moroder, L., Hojo, H.,* Inaba, K.,* and Iwaoka, M.*. Preparation of Selenoinsulin as a Long-Lasting Insulin Analogue. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 2017. 56. 20. 5522-5526

Ushioda, R., Miyamoto, A., Inoue, M., Watanabe, S., Okumura, M., Maegawa, K., Uegaki, K., Fujii, S., Fukuda, Y., Umitsu, M., Takagi, J., Inaba, K., Mikoshiba, K., and Nagata, K.* Redox-assisted regulation of Ca2+ homeostasis in the endoplasmic reticulum by ERdj5 Proc Natl Acad Sci USA., 2016. 113, E6055-E6063.

Kanemura, S., Okumura, M., Yutani, K., Ramming, T., Hikima, T., Appenzeller-Herzog, C., Akiyama, S., and Inaba, K.* Human Ero1α undergoes dual regulation through complementary redox interactions with PDI Journal of Biological Chemistry 2016 291, 23952-23964.

Ramming, T.,# Kanemura, S.,# Okumura, M., Inaba, K., and Appenzeller-Herzog, C.* Cysteines 208 and 241 in Ero1α are required for maximal catalytic turnover Redox Biol. 2016 7, 14-20.

Saiki, M.,* Shiba, K., and Okumura, M. Structural Stability of Amyloid Fibrils Depends on the Existence of the Peripheral Sequence near the Core Cross-03B2 Region FEBS Lett 2015 589, 3541-3547.

Ramming, T., Okumura, M., Kanemura, S., Baday, S., Birk, J., Moes, S., Jenö, P., Bernèche, S., Inaba, K., and Appenzeller-Herzog, C.* A PDI-catalyzed thiol/disulfide switch regulates the production of hydrogen peroxide by human Ero1 Free Radic Biol Med., 2015 83, 361-372.

Okumura, M.,# Kadokura, H.,# and Inaba, K.* Structural and mechanistic basis of the PDI family members producing disulfides within the ER Free Radic Biol Med., 2015 83, 314-322.

Murata, A., Ito, Y., Kashima, R., Kanbayashi, S., Nanatani, K., Igarashi, C., Okumura, M., Inaba, K., Tokino, T., Takahashi, S.,* and Kamagata, K.* One-dimensional sliding of p53 along DNA is accelerated in the presence of Ca2+ or Mg2+ at millimolar concentrations J. Mol Biol., 2015 427, 2663-2678.

Okumura, M.,* Kadokura, H., Hashimoto, S., Kanemura, S., Yutani, K., Hikima, T., Hidaka, Y., Ito, L., Shiba, K., Masui, S., Imai, D., Imaoka, S., Yamaguchi, H.,* and Inaba, K.* Endocrine disruptor driven conformational changes in protein disulfide isomerase J. Biol. Chem., 2014 289, 27004-27018.

Kojima, R.,# Okumura, M.,# Masui, S., Kanemura, S., Inoue, M., Saiki, M., Yamaguchi, H., Hikima, T., Suzuki, M., Akiyama S., and Inaba, K.* Radically different thioredoxin domain arrangement of ERp46, an efficient disulfide-bond introducer of the mammalian PDI family Structure. 2014 22, 431-443.

Okumura, M., Shimamoto, S., and Hidaka, Y.* Disulfide-mediated Peptide and Protein Folding Current Protocols in Protein Science, 2014 doi; 10.1002/0471140864.ps2807s76. John Wiley ＆ Sons, Inc.

Shimamoto, S., Katayama, H., Okumura, M., and Hidaka, Y.* Chemical Methods and Approaches to the Regioselective Formation of Multiple Disulfide Bond. Current Protocols in Protein Science, 2014 doi; 10.1002/0471140864.ps2808s76. John Wiley & Sons, Inc.

Sato, Y.,# Kojima, R.,# Okumura, M.,# Hagiwara, M.,# Masui, S., Maegawa, K., Saiki, M., Horibe, T., Suzuki, M., and Inaba, K.* PDI-family member proteins synergize to enhance the rate and fidelity of peroxiredoxin-4-driven oxidative protein folding Scientific Reports 2013 3 2456, Doi; 10.1038/srep02456.

Okumura, M., Shimamoto, S., and Hidaka, Y.* A Chemical Method for Investigating Disulfide-coupled Peptide and Protein Folding FEBS J., 2012 279, 2283-2295.

Okumura, M., Shimamoto, S., Nakanishi, T., Yoshida, Y., Konogami, T., Maeda, S., and Hidaka, Y.* Effects of positively charged redox molecules on disulfide-coupled protein folding. FEBS Lett., 2012 586(21):3926-30.

Ito, L.,* Okumura, M., Tao, K., Kasai, Y., Tomita, S., Oosuka, A., Yamada, H., Shibano, T., Shiraki, K., Kumasaka, T., and Yamaguchi, H.* Glutathione Ethylester, a Novel Protein Refolding Reagent, Enhances both the Efficiency of Refolding and Correct Disulfide Formation. The Protein J. 2012 499-503.

Hashimoto, S., Ito, L., Okumura, M., Shibano, T., Nawata, M., Kumasaka, T., Yamaguchi, H., and Imaoka, S.* Crystallization and preliminary crystallographic analysis of the complex between triiodothyronine and the bb’ fragment of rat protein disulfide isomerase. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 68(Pt 4):476-8.

Okumura, M., Saiki, M., Yamaguchi, H., and Hidaka, Y.* Acceleration of Disulfide-Coupled Protein Folding Using Glutathione Derivatives. FEBS J., 2011 278, 1137-1144.

金村進吾、稲葉謙次、奥村正樹 小胞体ジスルフィド結合形成ネットワークを支える酵素群の構造基盤、日本結晶学会誌 64 (3), 209-210, 2022

金村進吾、松﨑元紀、前仲勝美、稲葉謙次、奥村正樹 小胞体におけるMHCの品質管理、臨床免疫・アレルギー科 74 (5) 1-8 2020

奥村正樹、稲葉謙次 高速原子間力顕微鏡により明らかにされたプロテインジスルフィドイソメラーゼ(PDI)の構造ダイナミクス、生化学、pp107-112 2020

奥村正樹、稲葉謙次 高速原子間力顕微鏡を用いた酵素の触媒機構の可視化:PDIファミリーを例に、北隆館、月間「細胞」構造生物学の最前線pp47-52 2019

奥村正樹、稲葉謙次 PDI ファミリー酵素群の構造ダイナミクスに基づく機能制御、北隆館、月刊「細胞」エレクトロンバイオダイナミクスが支える生命の生存戦略 pp41-46 2019

奥村正樹、稲葉謙次 放射光利用の手引きー農水産・医療、エネルギー、環境、材料開発分野などへの応用ー細胞のタンパク質の立体構造を頑強にする仕組み、アグネ技術センター 2019

Okumura, M., Watanabe, S., and Inaba, K. Structural insights into disulphide bond formation and protein quality control in the mammalian ER　Oxidative Folding of Peptides and Proteins, (RSC) chapter3.3., p224 – 248、2018

奥村正樹、稲葉謙次 PDIファミリー酵素による小胞体のタンパク質品質管理機構、pp133-143、アルツハイマー病ー発症メカニズムと新規診断法・創薬・治療開発 2018

金村進吾、奥村正樹、稲葉謙次 X線小角散乱解析が明らかにしたPDIファミリータンパク質ERp46及びPDI酸化酵素Ero1αの構造ダイナミクスと機能、分子研レターズ 2017

奥村正樹、稲葉謙次 ERp46とPDIの異なる構造と機能的役割、日本生物物理学会誌、pp34-36 2015

奥村正樹、稲葉謙次 哺乳動物細胞の小胞体におけるジスルフィド結合形成ネットワークの構造基盤、羊土社、pp208-215 2014

奥村正樹、日高雄二 グルタチオン誘導体を用いたジスルフィド結合含有蛋白質の立体構造形成の促進、遺伝子医学 メディカルドゥ社、pp192-198 2012

特願2022-031958

PCT/JP2021/21437

特願2021-033583

特願2020-100517

特願2018-109769

特願2010-270195