Elucidating plasma effect on structural modification of antioxidant enzymes: Combined experimental and computational

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K14454
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 14030:Applied plasma science-related
• Research Institution: Kyushu University
• Principal Investigator: Attri Pankaj 九州大学, プラズマナノ界面工学センター, 准教授 (40868361)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Protein folding / MD Simulation / Biophysical studies

Outline of Final Research Achievements

Target 1: Structural modification of NADPH oxidase activator (Noxa 1) by oxidative stress: An experimental and computational study. In this work, we demonstrate the effect of plasma effect on the structural changes of Noxa1 SH3 protein, one of the regulatory subunits of NOX1. The structural deformation of Noxa1 SH3 protein was analyzed by various experimental methods and by MD simulations. Target 2: Possible impact of plasma oxidation on the structure of C-terminal Domain of SARS-CoV-2 spike protein: A computational study. We checked the plasma effect on the structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike protein and interaction SARS-CoV-2-CTD with human Angiotensin-Converting Enzyme 2 (hACE2). Target 3: In this study we investigated the structural changes in Mdm2, p53, and the Mdm2-p53 before and after possible plasma oxidation through molecular dynamic (MD) simulations.

Free Research Field

Applied Plasma research

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義はプラズマ照射へのがん細胞の応答機序解明にある。我々はプラズマ処理によるNADPHオキシダーゼ・アクチベーター・プロテインとリゾチームの構造変化はアミノ酸の酸化によると示した。続いてSARS-CoV-2-CTDタンパク質の構造がプラズマ処理により不安定化し、酸化の抑制が結合自由エネルギーの減少に寄与すること、さらにプラズマで酸化されたMdm2はp53を阻害しないことを計算から示した。つまりプラズマ処理したがん細胞内の活性酸素の増加はp53によるカタラーゼの不活性化が原因と考えられる。以上の成果は新薬やワクチン、診断薬、治療薬の開発に繋がり、人類の健康へ貢献可能と期待できる。