6T05

Crystal structure of YTHDC1 with fragment 18 (DHU_DC1_048)

6T05 の概要

• エントリーDOI: 10.2210/pdb6t05/pdb
• 分子名称: YTHDC1, SULFATE ION, 2-(phenylmethyl)imidazolidine, ... (4 entities in total)
• 機能のキーワード: fragment, complex, ythdc1, epitranscriptomic, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 42835.16

構造登録者

Bedi, R.K.,Huang, D.,Sledz, P.,Caflisch, A. (登録日: 2019-10-02, 公開日: 2020-03-04, 最終更新日: 2024-01-24)

主引用文献

Bedi, R.K.,Huang, D.,Wiedmer, L.,Li, Y.,Dolbois, A.,Wojdyla, J.A.,Sharpe, M.E.,Caflisch, A.,Sledz, P.
Selectively Disrupting m6A-Dependent Protein-RNA Interactions with Fragments.
Acs Chem.Biol., 15:618-625, 2020

PubMed Abstract: We report a crystallographic analysis of small-molecule ligands of the human YTHDC1 domain that recognizes N6-methylated adenine (mA) in RNA. The 30 binders are fragments (molecular weight < 300 g mol) that represent 10 different chemotypes identified by virtual screening. Despite the structural disorder of the binding site loop (residues 429-439), most of the 30 fragments emulate the two main interactions of the -NHCH group of mA. These interactions are the hydrogen bond to the backbone carbonyl of Ser378 and the van der Waals contacts with the tryptophan cage. Different chemical groups are involved in the conserved binding motifs. Some of the fragments show favorable ligand efficiency for YTHDC1 and selectivity against other mA reader domains. The structural information is useful for the design of modulators of mA recognition by YTHDC1.

PubMed: 32101404
DOI: 10.1021/acschembio.9b00894

実験手法

X-RAY DIFFRACTION (1.5 Å)