Discovery of GATA3 DNA binding domain inhibitors using NMR-based study
GATA3 is a key transcription factor for type 2 immune responses. It regulates Th2 cell differentiation, and the transcription of inflammatory cytokines associated with allergic diseases. GATA3 contains two zinc finger domains, and this study focuses on the C-terminal zinc finger domain (ZnF2), which directly binds to DNA. If the interaction between the GATA3 and DNA were regulated, it could suppress cytokine transcription. Accordingly, we hypothesized that allergic immune diseases could be treated by regulating this interaction. In this study was conducted to determine the NMR structure of the GATA3 DNA binding domain. It also aimed to discover natural compounds through NMR-based screening to assess whether GATA3 is a potential target for allergic diseases. Based on NMR spectra, we assigned backbone and identified binding sites. We analyzed the interactions with natural compounds through chemical shift perturbation measurements. Additionally, the binding modes were confirmed via in silico docking simulation. Discovery of the novel GATA3 inhibitors targeting the DNA binding interface is expected to contribute to the development of new therapeutic strategies for chronic allergic diseases.
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