Wilson Jonathan R, Jing Chun, Walker Philip A, Martin Stephen R, Howell Steven A, Blackburn G Michael, Gamblin Steven J, Xiao Bing
Structural Biology Group, National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom.
Cell. 2002 Oct 4;111(1):105-15. doi: 10.1016/s0092-8674(02)00964-9.
Methylation of lysine residues in the N-terminal tails of histones is thought to represent an important component of the mechanism that regulates chromatin structure. The evolutionarily conserved SET domain occurs in most proteins known to possess histone lysine methyltransferase activity. We present here the crystal structure of a large fragment of human SET7/9 that contains a N-terminal beta-sheet domain as well as the conserved SET domain. Mutagenesis identifies two residues in the C terminus of the protein that appear essential for catalytic activity toward lysine-4 of histone H3. Furthermore, we show how the cofactor AdoMet binds to this domain and present biochemical data supporting the role of invariant residues in catalysis, binding of AdoMet, and interactions with the peptide substrate.
组蛋白N端尾部赖氨酸残基的甲基化被认为是调节染色质结构机制的重要组成部分。进化上保守的SET结构域存在于大多数已知具有组蛋白赖氨酸甲基转移酶活性的蛋白质中。我们在此展示了人SET7/9大片段的晶体结构，该片段包含一个N端β折叠结构域以及保守的SET结构域。诱变鉴定出该蛋白质C端的两个残基，它们对于组蛋白H3赖氨酸-4的催化活性似乎至关重要。此外，我们展示了辅因子AdoMet如何结合到该结构域，并提供了生化数据支持不变残基在催化、AdoMet结合以及与肽底物相互作用中的作用。
