Identification of a specific inhibitor of the Dishevelled PDZ domain
作者： Jufang Shan , De-Li Shi , Junmei Wang , Jie Zheng
DOI: 10.1021/BI0512602
关键词:
摘要: The Wnt signaling pathways are involved in embryo development as well tumorigenesis. Dishevelled (Dvl) transduces signals from the receptor Frizzled (Fz) to downstream components canonical and noncanonical pathways. Dvl PDZ domain is thought play an essential role both pathways, we recently demonstrated that binds directly Fz receptors. In this study, using structure-based virtual ligand screening, identified organic molecule (NSC668036) National Cancer Institute small-molecule library can bind domain. We then used molecular dynamics simulation analyze binding between NSC668036 detail. addition, showed that, Xenopus, expected, inhibited induced by Wnt3A. This compound provides a basis for rational design of high-affinity inhibitors domain, which block interrupting Fz-Dvl interaction.
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