9QZL

Structure of NONO bound to (R)-SKBG-1 in P43212

This is a non-PDB format compatible entry.

Summary for 9QZL

• Entry DOI: 10.2210/pdb9qzl/pdb
• Descriptor: Non-POU domain-containing octamer-binding protein, 4-(2-chloranylethanoyl)-~{N}-[(4-methoxyphenyl)methyl]-1-(4-methoxyphenyl)sulfonyl-piperazine-2-carboxamide (2 entities in total)
• Functional Keywords: dbhs, paraspeckle, ligand, rna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 61287.00

Authors

Fribourg, S. (deposition date: 2025-04-23, release date: 2025-12-17, Last modification date: 2026-07-01)

Primary citation

Florio, A.V.,Bure, C.,Fribourg, S.
Structural basis for NONO-specific modification by the alpha-chloroacetamide compound (R)-SKBG-1.
Cell Chem Biol, 33:268-275.e3, 2026

PubMed Abstract: Among the many proteins involved in cancer progression, an increasing number of RNA-binding proteins (RBPs) are central to the function of a cell and tightly associated to genetic diseases. In a recent study, small-molecule inhibitors have been identified as targeting NONO, an RBP known to be involved in mRNA splicing, DNA repair, and membraneless organelle stability. Here, we report the molecular basis of NONO targeting by the α-chloroacetamide molecule (R)-SKBG-1, its specific binding to NONO, and the enantiomer selectivity on the basis of mass spectrometry measurements and structure determination. We have determined the crystal structure of (R)-SKBG-1-bound to NONO homodimer. This study sheds light on the conformational plasticity of (R)-SKBG-1 when covalently bound to NONO. Altogether, these results give an experimental rationale for ligand modification and optimization in a future use as a drug against cancer.

PubMed: 41519128
DOI: 10.1016/j.chembiol.2025.12.013

Experimental method

X-RAY DIFFRACTION (2.9 Å)