2022 Fiscal Year Final Research Report
Elucidation of catalytic and maturation mechanisms of dicopper enzyme tyrosinase and the development of the inhibitors
Project/Area Number |
20K05715
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 37010:Bio-related chemistry
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Research Institution | Yasuda Women's University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | チロシナーゼ / 銅イオン / 反応機構 / 成熟化 |
Outline of Final Research Achievements |
The aim of this study is to elucidate the catalytic and maturation mechanisms of dicopper enzyme tyrosinase (Ty) using the complex formed between the Streptomyces Ty and its metallochaperone caddie protein (Cad). While Ty catalyzes both phenolase and catecholase reactions, catechol oxidase (CO) catalyzes only the latter reaction. The ability of the substrates to dissociate the motif shielding the active-site pocket seems to contribute critically to the substrate specificity of Ty. In addition, the increased basicity of the active-site water molecule was found to be necessary for the efficient phenolase reaction. On the other hand, zinc ions are thought to be bound to active site of Ty before the maturation. The oxidation of the Tyr98 residue of Cad after the replacement to the copper ions and the following release of Cad are likely important to stimulate the maturation.
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Free Research Field |
生体関連化学
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Academic Significance and Societal Importance of the Research Achievements |
本研究の成果として、Tyの基質結合部位を覆うシールドモチーフが存在しているとき、カテコール基質に比べ、フェノール基質の方が相対的に結合しにくくなることが示された。このことは、カテコール基質の基質結合部位への侵入によってシールドモチーフが遊離することが、Tyのフェノラーゼ活性のために重要であることを示唆する。同様に、銅イオンが取り込まれるTyの成熟化過程においても、成熟化後にシールドモチーフが遊離することが、効率的な銅イオンの取り込みに重要であることが示された。これらの知見は、様々な過程で働くTy阻害剤を開発するために役立つと考えられる。
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