6L1F

Crystal structure of PHF20L1 Tudor1 in complex with K142me1 DNMT1

6L1F の概要

• エントリーDOI: 10.2210/pdb6l1f/pdb
• 分子名称: the K142me1 DNMT1 peptide, PHD finger protein 20-like protein 1 (3 entities in total)
• 機能のキーワード: phf20l1, tudor, apo, metal binding protein-peptide complex, metal binding protein/peptide
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 9357.51

構造登録者

Lv, M.Q.,Gao, J. (登録日: 2019-09-29, 公開日: 2020-09-23, 最終更新日: 2023-11-22)

主引用文献

Lv, M.,Gao, J.,Li, M.,Ma, R.,Li, F.,Liu, Y.,Liu, M.,Zhang, J.,Yao, X.,Wu, J.,Shi, Y.,Tang, Y.,Pan, Y.,Zhang, Z.,Ruan, K.
Conformational Selection in Ligand Recognition by the First Tudor Domain of PHF20L1.
J Phys Chem Lett, 11:7932-7938, 2020

PubMed Abstract: The first Tudor domain (Tudor1) of PHF20L1 recognizes (non)histone methylation to play versatile roles. However, the underlying ligand-recognition mechanism remains unknown as a closed state revealed in the free-form structure. NMR relaxation dispersion and molecular dynamics simulations suggest a pre-existing low-population conformation with a remarkable rearrangement of aromatic cage residues of PHF20L1 Tudor1. Such an open-form conformation is utilized to recognize lysine 142 methylated DNMT1, a cosolvent, and an NMR fragment screening hit, as revealed by the complex crystal structures. Intriguingly, the ligand binding capacity was enhanced by mutation that tunes up the open-state population only. The recognition of DNMT1 by PHF20L1 was further validated in cancer cells. This conformational selection mechanism will enable the discovery of small molecule inhibitors against the seemingly "undruggable" PHF20L1 Tudor1.

PubMed: 32885980
DOI: 10.1021/acs.jpclett.0c02039

実験手法

X-RAY DIFFRACTION (1.9 Å)