4HON

Crystal structure of human JMJD2D/KDM4D in complex with an H3K9me3 peptide and 2-oxoglutarate

4HON の概要

• エントリーDOI: 10.2210/pdb4hon/pdb
• 分子名称: Lysine-specific demethylase 4D, Histone H3 Peptide, 2-OXOGLUTARIC ACID, ... (9 entities in total)
• 機能のキーワード: jumonji c demethylase, jmjd2/kdm4 family, beta barrel fold, oxidoreductase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : Q6B0I6
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 80330.14

構造登録者

Krishnan, S.,Trievel, R.C. (登録日: 2012-10-22, 公開日: 2012-11-21, 最終更新日: 2023-09-20)

主引用文献

Krishnan, S.,Trievel, R.C.
Structural and Functional Analysis of JMJD2D Reveals Molecular Basis for Site-Specific Demethylation among JMJD2 Demethylases.
Structure, 21:98-108, 2013

PubMed Abstract: JMJD2 lysine demethylases (KDMs) participate in diverse genomic processes. Most JMJD2 homologs display dual selectivity toward H3K9me3 and H3K36me3, with the exception of JMJD2D, which is specific for H3K9me3. Here, we report the crystal structures of the JMJD2D⋅2-oxoglutarate⋅H3K9me3 ternary complex and JMJD2D apoenzyme. Utilizing structural alignments with JMJD2A, molecular docking, and kinetic analysis with an array of histone peptide substrates, we elucidate the specific signatures that permit efficient recognition of H3K9me3 by JMJD2A and JMJD2D, and the residues in JMJD2D that occlude H3K36me3 demethylation. Surprisingly, these results reveal that JMJD2A and JMJD2D exhibit subtle yet important differences in H3K9me3 recognition, despite the overall similarity in the substrate-binding conformation. Further, we show that H3T11 phosphorylation abrogates demethylation by JMJD2 KDMs. Together, these studies reveal the molecular basis for JMJD2 site specificity and provide a framework for structure-based design of selective inhibitors of JMJD2 KDMs implicated in disease.

PubMed: 23219879
DOI: 10.1016/j.str.2012.10.018

実験手法

X-RAY DIFFRACTION (1.799 Å)