Concerted proton/electron transfer mechanism in cofactor-dependent enzyme

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K05573
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Osaka Medical College
• Principal Investigator: HAYASHI Hideyuki 大阪医科大学, 医学部, 教授 (00183913)
• Co-Investigator(Kenkyū-buntansha): 村川 武志 大阪医科大学, 医学部, 助教 (90445990)
• Research Collaborator: SHOJI mitsuo
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 酵素反応機構 / プロトン移動 / 電子移動 / エネルギー準位図 / 反応駆動力 / X線結晶解析 / 反応速度論 / 補欠分子族

Outline of Final Research Achievements

Enzymes, which are the catalysts for the chemical processes in living cells, promote the movements of protons and electrons. However, not much effort has been paid for elucidating the origin of the driving forces for these movements. In this study, a methodology was developed in order to clarify the driving force for the most probable reaction pathway. In this methodology, the reaction intermediates with all possible protonation and redox states are first classified according to the numbers of protons and electrons, and then the energy level is plotted against the coordinates of the reaction step, protonation state, and the redox state. The obtained energy landscape can be used to draw the reaction pathway, and combined with high-resolution structural methods, elucidate the structural elements of the driving force for the proton and electron movements.

Free Research Field

生体関連化学

Academic Significance and Societal Importance of the Research Achievements

今までの酵素反応機構の研究は現象の追跡に終始していたが，本研究はその現象がどのような力によってもたらされているかという，本質的な要因を明確にする方法論を確立したところに学術的な意義がある．また，この方法論によって酵素反応機構を明らかにする研究の方向性が明確になることは，現在，洗剤などの日常生活から薬品や各種素材の製造といった工業分野に至るまで酵素の触媒能力が応用されている領域において，望みの機能を持った酵素の開発を容易にすることにつながるという社会的意義がある．