2021 Fiscal Year Final Research Report
Reaction mechanism study of heme containing dioxygenase by stopped-flow resonance Raman spectroscopy
| Project/Area Number |
19K05698
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 37010:Bio-related chemistry
|
|---|
| Research Institution | University of Hyogo |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | ヘム酵素 / 二原子酸素添加酵素 / ストップトフロー / 共鳴ラマン / 免疫抑制 |
|---|
| Outline of Final Research Achievements |
Indoleamine 2,3-dioxygenase, which is a heme conatining enzyme, incorporates two oxygen atoms into Tryptophan. This reaction is the only dioxygenase reaction catalized by heme enzyme. On the other hand, this reaction is involved in immune suppression, and thus IDO is a immunotherapeutic target. However, the reaction mechanism of IDO is not yet fully understood. In this study, we monitored a whole enzymatic reaction by spectroscopy and asigned the structure and state of reaction intermediates to understand the reaction mechanism. As a result, a presence of two different types of ternary complex intermediates and the importance of a high reactivity of Trp are suggested.
|
| Free Research Field |
生物物理学、生物無機化学
|
| Academic Significance and Societal Importance of the Research Achievements |
IDOは免疫療法のターゲットであり、治療薬としてのIDO阻害剤の探索が盛んに行われている。本研究では、既報の中間体が２状態存在し時間経過に伴って増減する様子を捉え、また、この中間体の安定化の原因を示唆した。中間体が安定に存在することは、活性を低下させる要因であり、阻害剤をデザインする上で有益な情報といえる。同時に、ヘム酵素による唯一のニ原子酸素添加反応の反応機構解明の鍵となる、未検出中間体を検出するための実験をデザインする上でも有益な情報である。
|
