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

ABSTRACT: 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).

SUBMITTER: Kim Y 

PROVIDER: S-EPMC11866408 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature