Regulation of heme oxygenase-2 activity elucidated by the analysis of structural dynamics

2016 Fiscal Year Final Research Report

• Project/Area Number: 26840040
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Yokohama City University (2015-2016); Suntory Foundation for Life Sciences (2014)
• Principal Investigator: Furukawa Ayako 横浜市立大学, 生命医科学研究科, 特任助教 (90453050)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 動的構造解析 / 酵素

Outline of Final Research Achievements

Heme oxygenase-2 (HO-2) is composed of a structured region including the heme-binding site and a C-terminal disordered region.However, the C-terminal region's role in the activity is elusive and is difficult to explain by the crystal structure alone because it is disordered. We hypothesized that the C-terminal region transiently interacts with the structured region to regulate the structural dynamics responsible for the activity. To test this hypothesis, we have examined the enzyme activity and structural dynamics of two HO-2 constructs with (long HO-2) and without (short HO-2) the C-terminal region. Enzyme activity assay showed that long HO-2 had 1.5 times higher activity than short HO-2. To explain the difference in the enzyme activity, we performed PRE, R2 dispersion, and CLEANEX-PM experiments. The results of these experiments suggest that the change of the fluctuating mode by the interaction with the C-terminal disordered region regulates the HO-2 activity.

Free Research Field

構造生物学