LOPAC library screening identifies suramin as a TRIM21 binder with a unique binding mode revealed by crystal structure.

• Tác giả: Yeojin Kim, Stefan Knapp, Andreas Krämer
• Ngôn ngữ: eng
• Ký hiệu phân loại: 674.12 Structure
• Thông tin xuất bản: United States : Acta crystallographica. Section F, Structural biology communications , 2025
• Bộ sưu tập: NCBI
• ID: 680193

Tóm tắt

Differential scanning fluorimetry screening of the Library of Pharmacologically Active Compounds (LOPAC) identified four hits for the PRYSPRY domain of the human E3 ligase tripartite motif-containing protein 21 (TRIM21). Isothermal titration calorimetry subsequently confirmed suramin as a binder with micromolar affinity. To further investigate the binding mechanism, mouse TRIM21 was used as a structural surrogate due to its improved protein stability and high sequence similarity to the human counterpart. A crystal structure of the complex refined at 1.3 Å resolution revealed a unique binding mode, providing new avenues for targeting TRIM21 and for the development of proteolysis-targeting chimeras (PROTACs).