Marabelli Chiara, Marrocco Biagina, Mattevi Andrea
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy.
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy.
Curr Opin Struct Biol. 2016 Dec;41:135-144. doi: 10.1016/j.sbi.2016.07.011. Epub 2016 Jul 26.
LSD1 was the first discovered histone demethylase. Using a flavin-dependent oxidative mechanism, LSD1 demethylates the N-terminal tail of histone H3 in the context of a variety of developmental processes. This functional complexity involves the association with nuclear factors and non-coding RNAs. A number of exciting studies are uncovering the bases of these specific and diverse molecular interactions, which occur both at catalytic and non-catalytic regions of the enzyme. Alternative splicing and post-translation modifications represent further layers for modulating this complex molecular network. By combining structural methods with the usage of chemically modified histones, it is becoming possible to visualize how LSD1 and associated co-repressors recognize the nucleosome. The enzyme clamps the nucleosomal particle through multivalent interactions mediated by the non-catalytic domains, which represent prospective sites for drug design.
赖氨酸特异性去甲基化酶1（LSD1）是首个被发现的组蛋白去甲基化酶。LSD1利用黄素依赖性氧化机制，在多种发育过程中使组蛋白H3的N端尾部去甲基化。这种功能复杂性涉及与核因子和非编码RNA的关联。一些令人兴奋的研究正在揭示这些特定且多样的分子相互作用的基础，这些相互作用发生在该酶的催化和非催化区域。可变剪接和翻译后修饰代表了调节这个复杂分子网络的更多层面。通过将结构方法与化学修饰组蛋白的使用相结合，现在有可能可视化LSD1及相关共抑制因子如何识别核小体。该酶通过非催化结构域介导的多价相互作用夹住核小体颗粒，这些非催化结构域是药物设计的潜在靶点。
