6H1D

Crystal structure of C21orf127-TRMT112 in complex with SAH

6H1D の概要

• エントリーDOI: 10.2210/pdb6h1d/pdb
• 分子名称: HemK methyltransferase family member 2, Multifunctional methyltransferase subunit TRM112-like protein, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• 機能のキーワード: protein methyltransferase, histone methylation, complex, sah, gene regulation
• 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: 37001.47

構造登録者

Wang, S.,Hermann, B.,Metzger, E.,Peng, L.,Einsle, O.,Schuele, R. (登録日: 2018-07-11, 公開日: 2019-05-22, 最終更新日: 2025-12-10)

主引用文献

Metzger, E.,Wang, S.,Urban, S.,Willmann, D.,Schmidt, A.,Offermann, A.,Allen, A.,Sum, M.,Obier, N.,Cottard, F.,Ulferts, S.,Preca, B.T.,Hermann, B.,Maurer, J.,Greschik, H.,Hornung, V.,Einsle, O.,Perner, S.,Imhof, A.,Jung, M.,Schule, R.
KMT9 monomethylates histone H4 lysine 12 and controls proliferation of prostate cancer cells.
Nat.Struct.Mol.Biol., 26:361-371, 2019

PubMed Abstract: Histone lysine methylation is generally performed by SET domain methyltransferases and regulates chromatin structure and gene expression. Here, we identify human C21orf127 (HEMK2, N6AMT1, PrmC), a member of the seven-β-strand family of putative methyltransferases, as a novel histone lysine methyltransferase. C21orf127 functions as an obligate heterodimer with TRMT112, writing the methylation mark on lysine 12 of histone H4 (H4K12) in vitro and in vivo. We characterized H4K12 recognition by solving the crystal structure of human C21orf127-TRMT112, hereafter termed 'lysine methyltransferase 9' (KMT9), in complex with S-adenosyl-homocysteine and H4K12me1 peptide. Additional analyses revealed enrichment for KMT9 and H4K12me1 at the promoters of numerous genes encoding cell cycle regulators and control of cell cycle progression by KMT9. Importantly, KMT9 depletion severely affects the proliferation of androgen receptor-dependent, as well as that of castration- and enzalutamide-resistant prostate cancer cells and xenograft tumors. Our data link H4K12 methylation with KMT9-dependent regulation of androgen-independent prostate tumor cell proliferation, thereby providing a promising paradigm for the treatment of castration-resistant prostate cancer.

PubMed: 31061526
DOI: 10.1038/s41594-019-0219-9

実験手法

X-RAY DIFFRACTION (1.94 Å)