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

DOI: 10.1107/S2053230X25000913

Authors: Yeojin Kim (Goethe University Frankfurt) , Stefan Knapp (Goethe University Frankfurt) , Andreas Kramer (Goethe University Frankfurt)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section F Structural Biology Communications , VOL 81

State: Published (Approved)
Published: March 2025

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).

Journal Keywords: TRIM21; E3 ligases; crystal structure; suramin.

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography

Added On: 17/02/2025 09:21

Documents:
Acta Crystallographica F - 2025 - Kim - LOPAC library screening identifies suramin as a TRIM21 binder with a unique binding.pdf

Discipline Tags:

Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)