Mechanism and Control in Biological Amine Methylation

Abstract
Biological methylation is a subject that has fascinated mechanistically minded chemists for over 50 years. While early studies were usually directed at C‐methylation in natural products, more recent work on N‐methylation in DNA and proteins is being supported by the results of X‐ray crystallography. From this source, significant mechanistic detail can be gleaned and powerful insights gained into the nature of enzyme catalysis and selectivity in methyl‐transfer processes. The case of the human histone H3 transmethylase SET7/9 is considered in detail and compared to cognate histone lysine methylases. It provides an analysis of Nature's solution to the task of avoiding over‐methylation.