Does Cytochrome c Oxidase control proton-pump mechanism by small structural changes?

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K03794
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 13010:Mathematical physics and fundamental theory of condensed matter physics-related
• Research Institution: Kanagawa Institute of Technology
• Principal Investigator: Kamiya Katsumasa 神奈川工科大学, 公私立大学の部局等, 教授 (60436243)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: チトクロム酸化酵素 / 分子動力学

Outline of Final Research Achievements

Since the advent of abundant oxygen on Earth, organisms have acquired proteins such as oxidative enzymes and oxygen-addition enzymes, enabling the combustion of organic matter and hydroxylation utilizing oxygen. The aim of this study is to elucidate the structural basis that enables proteins such as cytochrome oxidases, which were acquired through the evolutionary process for organisms on Earth to use oxygen, to efficiently utilize oxygen. As a result of this study, it was suggested that minor distortions in the structure near the surface of cytochrome oxidase can propagate to the internal oxygen molecule transport pathway within the protein. Furthermore, for cytochrome P450 that synthesizes steroid hormones, we clarified the mechanism by which differences in the spatial shape of the substrate binding site generate differences in oxygen addition capabilities.

Free Research Field

計算生物物理学

Academic Significance and Societal Importance of the Research Achievements

ヒトのチトクロム酸化酵素は、進化の過程で細菌などの原核生物がもつ酵素に付加的なサブユニットが加わったため、近年ではサブユニット付近の結合を狙った抗菌剤の創薬標的の1つとしても注目されている。本研究で得られた知見は合理的な抗菌剤の開発に寄与することが期待される。また、ステロイドホルモンを合成するチトクロムP450に対して得られた本研究の知見は、ステロイドホルモンの過剰産生で起こる疾患に対する選択性の高い阻害剤の開発に寄与することが期待される。