Elucidation of the mechanism by which virus inhibits the function of human anti-virus enzymes and molecular basis of drug discovery

2017 Fiscal Year Final Research Report

• Project/Area Number: 26440026
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Kyoto University
• Principal Investigator: Nagata Takashi 京都大学, エネルギー理工学研究所, 准教授 (10415250)
• Co-Investigator(Renkei-kenkyūsha): TAKAORI Akifumi 京都大学, 医学部附属病院, 教授 (20324626) ; KATAHIRA Masato 京都大学, エネルギー理工学研究所, 教授 (60265717)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: Vif / APOBEC / アプタマー / NMR

Outline of Final Research Achievements

We have developed a stable-isotope labeling method of the Vif complex, which contains five proteins. Our method is capable of labeling either Vif or CBFβ, while the rest of the components are unlabeled. Obtained labeled Vif complex can be used to identify the binding sites of the anti-HIV proteins (A3F, A3G, etc.) and anti-Vif compounds on the Vif complex. We also obtained the RNA aptamers that bind to the Vif complex with high affinity. On the other hand, we investigated the influence of the DNA sequence/length and pH on deaminase activity, as well as the roles of the amino acid residues around the catalytic center of APOBEC3F. We newly found that the Vif complex inhibits the catalytic activity of the C-terminal domain of A3G. Our efforts will provide the tools for anti-Vif drug development.

Free Research Field

構造生命科学