7YYE

Orthorombic crystal structure of YTHDF1 YTH domain (G459N mutant) form I

7YYE の概要

• エントリーDOI: 10.2210/pdb7yye/pdb
• 分子名称: YTH domain-containing family protein 1, 1,2-ETHANEDIOL, MALONIC ACID, ... (4 entities in total)
• 機能のキーワード: mrna binding and stability, rna binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93459.01

構造登録者

Dalle Vedove, A.,Cazzanelli, G.,Lolli, G. (登録日: 2022-02-17, 公開日: 2023-03-01, 最終更新日: 2024-03-13)

主引用文献

Cazzanelli, G.,Dalle Vedove, A.,Spagnolli, G.,Terruzzi, L.,Colasurdo, E.,Boldrini, A.,Patsilinakos, A.,Sturlese, M.,Grottesi, A.,Biasini, E.,Provenzani, A.,Quattrone, A.,Lolli, G.
Pliability in the m 6 A-Binding Region Extends Druggability of YTH Domains.
J.Chem.Inf.Model., 2024

PubMed Abstract: Epitranscriptomic mRNA modifications affect gene expression, with their altered balance detected in various cancers. YTHDF proteins contain the YTH reader domain recognizing the mA mark on mRNA and represent valuable drug targets. Crystallographic structures have been determined for all three family members; however, discrepancies are present in the organization of the mA-binding pocket. Here, we present new crystallographic structures of the YTH domain of YTHDF1, accompanied by computational studies, showing that this domain can exist in different stable conformations separated by a significant energetic barrier. During the transition, additional conformations are explored, with peculiar druggable pockets appearing and offering new opportunities for the design of YTH-interfering small molecules.

PubMed: 38417111
DOI: 10.1021/acs.jcim.4c00051

実験手法

X-RAY DIFFRACTION (2 Å)