Significance of the presence of IDP enzyme and insight into structure for

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19282
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Kumeta Hiroyuki 北海道大学, 先端生命科学研究院, 学術専門職 (00399966)
• Co-Investigator(Kenkyū-buntansha): 姚 閔 北海道大学, 先端生命科学研究院, 名誉教授 (40311518) ; 尾瀬 農之 北海道大学, 先端生命科学研究院, 教授 (80380525)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: NMR / 結晶構造解析 / IDP / CD / Native-MS

Outline of Final Research Achievements

Ionophore polyethers, which have diverse bioactivities derived from the polyether backbone, are widely used as antibiotics. However, the details of its ether ring formation mechanism were unknown. MonBI and MonBII are responsible for enzymatic ether cyclization in monensin biosynthesis. Previous studies have shown that MonBII, IDP of the catalyst, forms its structure and exerts its function with assistance of the chaperone molecule MonBI. This paired enzyme model has been suggested to be widely conserved in other epoxide hydrolases and may generalize the polyether biosynthesis pathway. In this study, I analyzed the properties of MonBI and MonBII by structural and spectroscopic methods. I have successfully shown that MonBI is highly soluble protein despite with large hydrophobic surface that is indispensable for a role as a chaperone.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

立体構造非形成蛋白質(IDP)はシグナル伝達経路に多く発見されているが，酵素全体がIDPである報告例は無かった。我々は本研究により，ポリエーテル系天然物生合成経路にはIDP酵素（MonBII型酵素）が存在することを，世界で初めて提示した。MonBIIがIDP酵素として存在する意義としては，形の異なった基質を認識するためのカメレオン的可塑性を発揮できることが挙げられる。確立した独自の素材・実験系をさらに応用すれば，蛋白質研究の根底命題であるフォールディング過程をNMRを用いてタイムラプス観測できると考えている。