Structure of the PRC2 complex and application to drug discovery

• Published in: Acta pharmacologica Sinica Vol. 38; no. 7; pp. 963 - 976
• Main Authors: Shi, Yi, Wang, Xiao-xi, Zhuang, You-wen, Jiang, Yi, Melcher, Karsten, Xu, H Eric
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2017; Nature Publishing Group
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer therapies; Cell cycle; Chromatin; DNA methylation; Drug Discovery; Epigenetics; Gene expression; Gene silencing; Histone H3; Humans; Immunology; Internal Medicine; Lysine; Medical Microbiology; Mutation; Neoplasms - drug therapy; Neoplasms - metabolism; Peptides; Pharmacology/Toxicology; Polycomb group proteins; Polycomb Repressive Complex 2 - antagonists & inhibitors; Polycomb Repressive Complex 2 - chemistry; Polycomb Repressive Complex 2 - metabolism; Proteins; R&D; Research & development; Review; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Vaccine; 体结构; 催化活性; 基因沉默; 复合物; 应用; 癌症治疗; 组蛋白H3; 药物发现; nucleosome; histone methyltransferase; PRC2; drug discovery; structure; H3K27me3
• ISSN: 1671-4083; 1745-7254; 1745-7254
• DOI: 10.1038/aps.2017.7

The polycomb repressive complexes 2 （PRC2） complex catalyzes tri-methylation of histone H3 lysine 27 （H3K27）, a repressive chromatin marker associated with gene silencing. Overexpression and mutations of PRC2 are found in a wide variety of cancers, making the catalytic activity of PRC2 an important target of cancer therapy. This review highlights recent structural breakthroughs of the human PRC2 complex bound to the H3K27 peptide and a small molecule inhibitor, which provide critically needed insight into PRC2-targeted drug discovery.