SNAP output for PDB entry 7z26 [SNAP web server]

PDB-id

7z26; SNAP-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein

Method

X-ray (1.9 Å)

Summary

Crystal structure of ythdf2 yth domain in complex with m6a RNA

Reference

Nai F, Nachawati R, Zalesak F, Wang X, Li Y, Caflisch A (2022): "Fragment Ligands of the m 6 A-RNA Reader YTHDF2." Acs Med.Chem.Lett., 13, 1500-1509. doi: 10.1021/acsmedchemlett.2c00303.

Abstract

We report 17 small-molecule ligands that compete with N6-methyladenosine (m₆A) for binding to the m₆A-reader domain of YTHDF2 (YT521-B homology domain family 2). We determined their binding mode at high resolution by X-ray crystallography and quantified their affinity by a fluorescence-based binding assay. 6-Cyclopropyluracil and a pyrazolopyrimidine derivative have favorable ligand efficiencies of 0.47 and 0.38 kcal mol_-1 per non-hydrogen atom, respectively. They represent useful starting points for hit optimization.