Drug development of African sleeping sickness targeting energy metabolic pathway

2016 Fiscal Year Final Research Report

• Project/Area Number: 26440027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: Shiba Tomoo 京都工芸繊維大学, 応用生物学系, 准教授 (80401206)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: トリパノソーマ / 顧みられない熱帯病 / エネルギー代謝 / 二核鉄タンパク質 / 膜表剤型タンパク質 / アスコフラノン / X線結晶構造解析

Outline of Final Research Achievements

The trypanosome cyanide-insensitive alternative oxidase (TAO) and trypanosome glycerol kinase (TGK) are drug targets for human African sleeping sickness. In this study, I determined the crystal structures of TAO and TGK in complex with its lead compounds to make more potent drug. The crystal structure of TAO in complex with its new inhibitor, ferulenol was determined at 2.7 Å resolution. I found GK-17b which is a novel inhibitor of TGK. In addition, this compound inhibits TAO enzymatic activity with comparable strength.

Free Research Field

構造生物化学