9JUR

Crystal Structure of NHL domain of human E3 ubiquitin-protein ligase TRIM71

9JUR の概要

• エントリーDOI: 10.2210/pdb9jur/pdb
• 分子名称: E3 ubiquitin-protein ligase TRIM71, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: nhl domain, e3 ubiquitin-protein ligase, rna binding, rna binding protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31729.97

構造登録者

Lv, M.Q.,Kazy, E.H. (登録日: 2024-10-08, 公開日: 2025-04-30)

主引用文献

Lin, L.,Hasan, M.K.E.,Gu, X.,Khan, S.U.,Hossain, A.,Faruqe, M.O.,Shahriar, S.,Joy, M.N.H.,Sourov, M.M.H.,Khan, M.I.,Zhang, L.,Lv, M.,Shi, Y.
Human tripartite motif-containing protein 71 NCL-1/HT2A/LIN-41 domain crystal structure and its potential natural inhibitors.
Int.J.Biol.Macromol., 309:142764-142764, 2025

PubMed Abstract: TRIM71 NHL Domain is a critical driver of various cellular process and is dysregulated in several medical conditions like non-small cell lung cancer, hepatocellular carcinoma and congenital hydrocephalus. However, its pathways and binding with CDKN1A has not been well studied. To investigate its interaction with CDKN1A, we expressed TRIM71 NHL domain in SF9 (Spodoptera frugiperda) insect cells using the pFastBacTM HT B plasmid, was purified by size exclusion chromatography and its crystal structure was determined successfully (PDB ID: 9JUR). Fluorescence polarization (Kd = 0.42 ± 0.04 μM) and EMSA confirmed strong and specific binding to CDKN1A mRNA, indicating its role in repressing CDKN1A expression to promote cancer cell proliferation. To further delve into its therapeutic implication, we screened a library of 2517 phytochemicals from 48 medicinal plants to identify potential natural inhibitors of the TRIM71 NHL domain. Epigallocatechin Gallate and Cyanidin 3-O-galactoside demonstrated binding affinities of -9.1 kcal/mol and -9.0 kcal/mol, respectively, while SPR confirmed their affinities with Kd values of 3.2 μM and 17.3 μM, accordingly. Molecular dynamics simulations confirmed protein-ligand complexes stability. In summary, human TRIM71 NHL domain crystal structure provides a foundation for understanding its structural features while exploring two potential inhibitors for therapeutic applications.

PubMed: 40180090
DOI: 10.1016/j.ijbiomac.2025.142764

実験手法

X-RAY DIFFRACTION (2.85 Å)