7Z26

Crystal structure of YTHDF2 YTH domain in complex with m6A RNA

Summary for 7Z26

Entry DOI	10.2210/pdb7z26/pdb
Descriptor	YTH domain-containing family protein 2, RNA (5'-R(P(6MZ)PCP*U)-3'), SULFATE ION, ... (5 entities in total)
Functional Keywords	epitranscriptomic reader, m6a reader, rna binding protein
Biological source	Homo sapiens (human) More
Total number of polymer chains	4
Total formula weight	42219.99
Authors	Nai, F.,Nachawati, R.,Li, Y.,Caflisch, A. (deposition date: 2022-02-25, release date: 2022-03-16, Last modification date: 2024-02-07)
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 Cited by 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 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (1.9 Å)

Structure validation