4QQK

Human HMT1 hnRNP methyltransferase-like protein 6 (S. cerevisiae) with GMS

4QQK の概要

• エントリーDOI: 10.2210/pdb4qqk/pdb
• 分子名称: Protein arginine N-methyltransferase 6, (5S)-5-{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}-N~6~-carbamimidoyl-L-lysine, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: hrmt1l6, protein arginine n-methyltransferase 6, structural genomics, structural genomics consortium, sgc, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : Q96LA8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42604.11

構造登録者

Dong, A.,Zeng, H.,He, H.,Wernimont, A.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Brown, P.J.,Min, J.,Luo, M.,Wu, H.,Structural Genomics Consortium (SGC) (登録日: 2014-06-27, 公開日: 2014-07-16, 最終更新日: 2024-10-30)

主引用文献

Wu, H.,Zheng, W.,Eram, M.S.,Vhuiyan, M.,Dong, A.,Zeng, H.,He, H.,Brown, P.,Frankel, A.,Vedadi, M.,Luo, M.,Min, J.
Structural basis of arginine asymmetrical dimethylation by PRMT6.
Biochem. J., 473:3049-3063, 2016

PubMed Abstract: PRMT6 is a type I protein arginine methyltransferase, generating the asymmetric dimethylarginine mark on proteins such as histone H3R2. Asymmetric dimethylation of histone H3R2 by PRMT6 acts as a repressive mark that antagonizes trimethylation of H3 lysine 4 by the MLL histone H3K4 methyltransferase. PRMT6 is overexpressed in several cancer types, including prostate, bladder and lung cancers; therefore, it is of great interest to develop potent and selective inhibitors for PRMT6. Here, we report the synthesis of a potent bisubstrate inhibitor GMS [6'-methyleneamine sinefungin, an analog of sinefungin (SNF)], and the crystal structures of human PRMT6 in complex, respectively, with S-adenosyl-L-homocysteine (SAH) and the bisubstrate inhibitor GMS that shed light on the significantly improved inhibition effect of GMS on methylation activity of PRMT6 compared with SAH and an S-adenosyl-L-methionine competitive methyltransferase inhibitor SNF. In addition, we also crystallized PRMT6 in complex with SAH and a short arginine-containing peptide. Based on the structural information here and available in the PDB database, we proposed a mechanism that can rationalize the distinctive arginine methylation product specificity of different types of arginine methyltransferases and pinpoint the structural determinant of such a specificity.

PubMed: 27480107
DOI: 10.1042/BCJ20160537

実験手法

X-RAY DIFFRACTION (1.88 Å)