Creation of functional proteins bearing highly modified unusual protein-derived cofactors

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19094
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 38:Agricultural chemistry and related fields
• Research Institution: Osaka Metropolitan University (2022); Osaka Prefecture University (2021)
• Principal Investigator: Fujieda Nobutaka 大阪公立大学, 大学院農学研究科, 教授 (00452318)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 補欠分子族 / 翻訳後化学修飾 / キノプロテイン

Outline of Final Research Achievements

Recently, the development of analytical techniques has led to the discovery of novel built-in coenzymes formed by post-translational chemical modification of amino acid residues in proteins, such as cysteinyl tyrosine in galactose oxidase (GAO). In our laboratory, we have studied the cupin protein from thermophilic bacteria, which has low molecular weight and a metal binding motif with four histidines. In this study, we prepared a copper-containing metalloprotein that mimics the environment of the active center of GAO by using this protein, and formed a Tyr-Cys cross-linked structure using this protein. Thus, by using saturated mutagenesis to two amino acid residues in the proximity of Tyr108, the crosslink formation of these mutant was further improved.

Free Research Field

生物無機化学

Academic Significance and Societal Importance of the Research Achievements

芳香族アミノ酸から生じる特殊な側鎖は配位子や補欠分子族として高度な機能を発揮するものがある。その機能は様々で他の有機補因子やカノニカルなアミノ酸残基にはない物理化学・触媒化学的に珍しい性質を示す。このように、今後、本研究結果を発展させ、様々な特殊なアミノ酸残基を形成させることができればタンパク質のさらなる機能化が期待される。