Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase.

Zhang, Xing; Tamaru, Hisashi; Khan, Seema I; Horton, John R; Keefe, Lisa J; Selker, Eric U; Cheng, Xiaodong · Cell · 2002

basic_science · Level V

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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.

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