6CEN

Crystal Structure of WHSC1L1 in Complex with Inhibitor PEP21

6CEN の概要

• エントリーDOI: 10.2210/pdb6cen/pdb
• 分子名称: Histone-lysine N-methyltransferase NSD3, ACE-GLY-VAL-NLE-ARG-ILE-NH2, S-ADENOSYLMETHIONINE, ... (5 entities in total)
• 機能のキーワード: histone-lysine n-methyltransferase nsd3, transferase, transferase-inhibitor complex, transferase/inhibitor
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : Q9BZ95
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27112.05

構造登録者

Boriack-Sjodin, P.A.,Swinger, K.,Farrow, N.A. (登録日: 2018-02-12, 公開日: 2018-05-09, 最終更新日: 2024-10-16)

主引用文献

Morrison, M.J.,Boriack-Sjodin, P.A.,Swinger, K.K.,Wigle, T.J.,Sadalge, D.,Kuntz, K.W.,Scott, M.P.,Janzen, W.P.,Chesworth, R.,Duncan, K.W.,Harvey, D.M.,Lampe, J.W.,Mitchell, L.H.,Copeland, R.A.
Identification of a peptide inhibitor for the histone methyltransferase WHSC1.
PLoS ONE, 13:e0197082-e0197082, 2018

PubMed Abstract: WHSC1 is a histone methyltransferase that is responsible for mono- and dimethylation of lysine 36 on histone H3 and has been implicated as a driver in a variety of hematological and solid tumors. Currently, there is a complete lack of validated chemical matter for this important drug discovery target. Herein we report on the first fully validated WHSC1 inhibitor, PTD2, a norleucine-containing peptide derived from the histone H4 sequence. This peptide exhibits micromolar affinity towards WHSC1 in biochemical and biophysical assays. Furthermore, a crystal structure was solved with the peptide in complex with SAM and the SET domain of WHSC1L1. This inhibitor is an important first step in creating potent, selective WHSC1 tool compounds for the purposes of understanding the complex biology in relation to human disease.

PubMed: 29742153
DOI: 10.1371/journal.pone.0197082

実験手法

X-RAY DIFFRACTION (1.61 Å)