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  • 03월 02일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제117회 대한화학회 학술발표회, 총회 및 기기전시회 안내 NMR studies of interaction between human dishevelled PDZ domain and its inhibitors

2016년 2월 24일 23시 53분 06초
BIO.P-303 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
4월 21일 (목요일) 11:00~12:30
저자 및
정영진, 이원태*
연세대학교 생화학과, Korea
Wnt signaling has important roles in embryonic development and tissue maintenance in adult. Moreover, clinical investigations demonstrate the positive roles of the Wnt/β-catenin pathway in osteoblast differentiation and bone mineral density maintenance. For the activation of Wnt/β-catenin signaling, dishevelled (Dvl) is a core protein and its PDZ domain transmits Wnt signals from Wnt receptor that bounded membrane to downstream molecules. Many research groups try to develop small-molecule inhibitors to block the protein-protein interaction on Dvl protein for the potential cancer-treatment and prevention agents. In our study, we characterized the protein-small molecule interaction effecting on regulation of osteoblast differentiation and bone formation through the Dvl PDZ domain. For the interaction study of Dvl PDZ domain with its inhibitory ligands, experiments were performed using nuclear magnetic resonance (NMR) spectroscopy and fluorescence spectroscopy. Backbone chemical shift assignments were completely done by 2D and 3D NMR spectrum analysis. In NMR titration experiment, residues located in α1 and β2 were revealed large chemical shift perturbation as considering inhibitor binding site. We also calculated binding affinities of Dvl PDZ domain and inhibitory ligands by titrating on fluorescence assay. Our results suggest that the inhibitors bind the Dvl PDZ domain through the α1 and β2 region as doing the domain’s native ligands and regulate the osteoblast differentiation and bone maintenance via blockade of the Dvl PDZ domain.