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.