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  • 09월 01일 18시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제118회 대한화학회 학술발표회, 총회 및 기기전시회 안내 A new strategy for inhibiting ubiquitin pathway using ubiquitin binding small molecules

2016년 9월 2일 14시 35분 10초
BIO1-3 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 14시 : 50분
생명화학 - Biochemistry of Proteostasis
저자 및
성균관대학교 의학과, Korea
The ubiquitin pathway plays a critical role in regulating diverse biological processes, and its dysregulation is associated with various diseases. Therefore, it is important to have a tool to control ubiquitin pathway for better understanding this pathway as well as developing therapeutics against relevant diseases. We found that sulfonated aryl diazo compounds could inhibit the ubiquitin processing enzymes involved in ubiquitination and deubiquitination, and cell surface receptor that recognizes ubiquitin as a ligand. NMR mapping, docking and molecular dynamics simulations reveal that these compounds block interactions between ubiquitin and cognate proteins by direct binding to the β-groove, a major interacting surfaces of ubiquitin. Furthermore, we found that cellular localization of compounds varies depending on the overall charges, and thus intracellular or extracellular ubiquitin-protein interactions can be controlled using the location specific inhibitors. Eventually, we demonstrated that these ubiquitin binding chemicals can effectively suppress the cancer progress, suggesting chemical-mediated inhibition of ubiquitin binding can be used for cancer therapy. Our results suggest that ubiquitin binding molecules can be developed as inhibitors of ubiquitin pathways, which have the value in not only unveiling the biological role of ubiquitin but also treating related diseases.