Structural basis for auto-inhibition mechanisms of MAP2K

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07897
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Osaka Prefecture University
• Principal Investigator: Kinoshita Takayoshi 大阪府立大学, 理学(系)研究科(研究院), 准教授 (90405340)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Ｘ線結晶構造解析 / キナーゼ / アロステリック阻害 / MAP2K

Outline of Final Research Achievements

High resolution crystal structure was achieved by the protein stabilization and crystallization in the space and depicted two auto-inhibition mechanisms. (1) The n-σ* interaction of Cys218 with Gly145 occluded the ATP site. (2) The C-terminal extension bound to the N-terminal region of the adjacent molecules and worked as a negative regulator. A synthesized C-terminal region peptide moderately attenuated the enzyme activity.

Free Research Field

構造生物学、創薬化学