Stilbenoids from Vitis amurensis Bind to the GATA-3 DNA-Binding Domain and Inhibit the Transcription by GATA-3
GATA-3 serves as a key transcription factor driving Th2 cell differentiation and allergic cytokine production. Identifying the natural modulators of GATA-3 could provide therapeutic opportunities for the regulation of allergic responses. This study aimed to identify Vitis amurensis-derived natural products with strong GATA-3 inhibition and to elucidate their binding modes and mechanisms of action. The DNA-binding domain 2 (DBD2) of human GATA-3 was analyzed by using NMR spectroscopy, including backbone assignment. Isolated natural compounds were screened for binding activity, followed by reporter gene assays to evaluate the transcriptional inhibition potential. Two-dimensional NMR and docking studies were conducted to characterize binding interactions and identify binding sites. Stilbenoids from V. amurensis showed specific binding to the DNA-binding domain of GATA-3, as detected by 2D NMR. Reporter gene assays revealed dose-dependent transcriptional inhibition by these compounds. One of the hit compounds, KUP149, exhibited two binding modes on DBD2 based on NMR data, both of which can disrupt GATA-3–DNA interactions. These findings suggest stilbene-based natural products as potential inhibitors of allergic immune responses via GATA-3 modulation.
