Aplysqualenol A Binds to the Light Chain of Dynein Type 1 (DYNLL1).
ABSTRACT A bidirectional affinity system has been developed for the identification of cancer-related natural products and their biological targets. Aplysqualenol A is thus selectively identified as a ligand of the dynein light chain. The use of forward and reverse affinity methods suggests that both small-molecule isolation and target identification can be conducted using conventional molecular biological methods.
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ABSTRACT: Triptolide (TP) is a biologically active diterpene triepoxide from the Chinese herb Tripterygium wilfordii Hook f. Here, we identify and explore TAB1 as the binding target of TP in macrophages by using a comprehensive approach combining pull-down assays, in vitro assessments, and pharmaceutical and biological evaluation. We discover that TP inhibits TAK1 kinase activity by interfering with the formation of the TAK1-TAB1 complex, and the binding affinity of TP to TAB1 correlates highly with the inhibitory activity of TP against MAPK pathway activation in macrophages. We also find that the amino acid sequence between positions 373 and 502 of TAB1 is required for TP interaction. Our results suggest that TP could be a selective small-molecule inhibitor of the TAK1-TAB1 complex and that TAB1 could be a potential therapeutic target in inflammatory disease.Chemistry & biology 01/2014; · 6.52 Impact Factor