7Z8W

Crystal structure of YTHDF2 with compound YLI_DC1_018

Summary for 7Z8W

• Entry DOI: 10.2210/pdb7z8w/pdb
• Descriptor: YTH domain-containing family protein 2, SULFATE ION, ~{N}-cyclopropyl-3-methyl-2~{H}-pyrazolo[4,3-d]pyrimidin-7-amine, ... (6 entities in total)
• Functional Keywords: epitranscriptomic reader, m6a reader, rna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 40091.43

Authors

Nai, F.,Li, Y.,Caflisch, A. (deposition date: 2022-03-18, release date: 2022-03-30, Last modification date: 2024-01-31)

Primary citation

Nai, F.,Nachawati, R.,Zalesak, F.,Wang, X.,Li, Y.,Caflisch, A.
Fragment Ligands of the m 6 A-RNA Reader YTHDF2.
Acs Med.Chem.Lett., 13:1500-1509, 2022

PubMed Abstract: We report 17 small-molecule ligands that compete with -methyladenosine (mA) for binding to the mA-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 per non-hydrogen atom, respectively. They represent useful starting points for hit optimization.

PubMed: 36110386
DOI: 10.1021/acsmedchemlett.2c00303

Experimental method

X-RAY DIFFRACTION (1.9 Å)