Crystallographic analysis of an anticancer target enzyme at high resolution

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06600
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Kumamoto University
• Principal Investigator: Nakamura Teruya 熊本大学, 大学院先導機構, 准教授 (40433015)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 構造生物学 / X線結晶構造解析 / 中性子結晶構造解析

Outline of Final Research Achievements

In this research, we investigated mechanisms of an enzymatic reaction and inhibitor binding of an oxidized nucleotide hydrolase. We carried out the crystallization under microgravity and determined the high-resolution crystal structure. The structure revealed the protonation state in the active site with higher accuracy and precision. In addition, we obtained structural insights into the substrate specificity of the hydrolase by experiments of X-ray crystallography, activity measurement, and substrate binding.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

酵素などのタンパク質の機能を原子レベルで理解するには、水素原子までをも明らかにする精密構造解析が必要不可欠である。本研究では、酸化ヌクレオチド加水分解酵素の精密構造解析を行うことで、酵素反応機構、阻害剤結合において重要な活性部位の水素原子を含めた構造情報を得た。