粗糙脉孢菌SET结构域蛋白DIM-5（一种组蛋白H3赖氨酸甲基转移酶）的结构
Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase.
作者信息
Zhang Xing, Tamaru Hisashi, Khan Seema I, Horton John R, Keefe Lisa J, Selker Eric U, Cheng Xiaodong
机构信息
Department of Biochemistry, School of Medicine, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA.
出版信息
Cell. 2002 Oct 4;111(1):117-27. doi: 10.1016/s0092-8674(02)00999-6.
Abstract
AdoMet-dependent methylation of histones is part of the "histone code" that can profoundly influence gene expression. We describe the crystal structure of Neurospora DIM-5, a histone H3 lysine 9 methyltranferase (HKMT), determined at 1.98 A resolution, as well as results of biochemical characterization and site-directed mutagenesis of key residues. This SET domain protein bears no structural similarity to previously characterized AdoMet-dependent methyltransferases but includes notable features such as a triangular Zn3Cys9 zinc cluster in the pre-SET domain and a AdoMet binding site in the SET domain essential for methyl transfer. The structure suggests a mechanism for the methylation reaction and provides the structural basis for functional characterization of the HKMT family and the SET domain.
摘要
依赖腺苷甲硫氨酸的组蛋白甲基化是“组蛋白密码”的一部分，可深刻影响基因表达。我们描述了粗糙脉孢菌DIM-5（一种组蛋白H3赖氨酸9甲基转移酶（HKMT））的晶体结构，分辨率为1.98埃，还介绍了关键残基的生化特性和定点诱变结果。这种SET结构域蛋白与先前表征的依赖腺苷甲硫氨酸的甲基转移酶没有结构相似性，但具有显著特征，如SET结构域前的三角Zn3Cys9锌簇和SET结构域中对甲基转移至关重要的腺苷甲硫氨酸结合位点。该结构揭示了甲基化反应的机制，并为HKMT家族和SET结构域的功能表征提供了结构基础。
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