High-resolution structural studies of electron transfer reaction mechanism in the redox cycle of NADH-cytochrome b5 reductase

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K07325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: HIRANO Yu 国立研究開発法人量子科学技術研究開発機構, 量子生命科学領域, 主幹研究員(定常) (80710772)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 中性子回折 / X線回折 / 酸化還元 / 高分解能

Outline of Final Research Achievements

High-resolution structural analyses were performed for NADH-cytochrome b5 reductase (b5R) and cytochrome b5 (b5) found in mammalian endoplasmic reticulum. The b5R and b5 redox system is involved in some metabolic processes including lipid synthesis. We have successfully determined high-resolution neutron and X-ray crystal structures for several redox states of b5R. The high-resolution structure analyses provide insights for understanding molecular mechanisms of the hydrogen movement that has important roles in the b5R redox cycle. Additionally, we could obtain high quality crystals of b5 with large volumes. Therefore, we will be able to perform high-resolution neutron structure analyses to visualize hydrogen atoms that have key roles in the b5 redox reaction.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

タンパク質の高分解能構造解析例は限られているが、X線と中性子両方の特徴を生かした高精度構造解析は、酸化還元酵素の機能理解において重要な手法である。本研究によって、b5Rとb5を対象として酸化還元反応系全体に高精度構造解析の領域を拡張でき、これまで断片的な情報に基づき議論されてきた酸化還元反応機構に対し新しい知見を提供できると考えられる。また酸化還元反応機構の詳細理解が進むことで、b5R-b5系の関与する疾患への治療方法開発のみならず、b5R、b5を含む酸化還元酵素を利用したバイオ燃料電池の電極材料開発といった応用研究への貢献も期待できる。