The analysis of transcriptional mechanism intermediated by a novel histone modification reader protein(Fostering Joint International Research)

2017 Fiscal Year Final Research Report

• Project/Area Number: 15KK0251
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: The University of Tokyo
• Principal Investigator: KANKI YASUHARU 東京大学, アイソトープ総合センター, 助教 (00534869)
• Research Collaborator: Subramaniam Sriram National Institute of Health, National Cancer Institute・Center for Cell Research・Laboratory of Cell Biology・Biophysics Section・High Resolution Electron Microscopy, Senior Director
• Project Period (FY): 2016 – 2017
• Keywords: クライオ電子顕微鏡 / ピルビン酸キナーゼ / 抗がん剤 / 単粒子解析

Outline of Final Research Achievements

Pyruvate kinase (PK) catalyzes the last irreversible step of glycolysis, and is known to be one of the rate-limiting enzyme of glycometabolism. There are four PK isoforms in mammals, PKM2 knockout lead to the reduction of cancer cell growth. Therefore, to elucidate the molecular mechanism of PKM2 enzymatic activity by atomic level is very valuable to develop a new drug on various kinds of cancer. In this project, we use the latest cryo-electron microscopy machine to resolve the atomic model of human PKM2 wild type and patient-derived mutant PKM2 H391Y. By using a single particle analysis, we clarified PKM2-WT, and PKM2-H391Y for the resolution of 2.9 Å and 3.1 Å, respectively. Taken together, we learned how to use a breakthrough technology in structural biology field in this international collaborating grant.

Free Research Field

ゲノム医科学