Chemical Biology of Protein N-Terminal Methyltransferases

Abstract

Protein α-N-terminal methylation is catalyzed by protein N-terminal methyltransferases. The prevalent occurrence of this methylation in ribosomes, myosin, and histones implies its function in protein-protein interactions. Although its full spectrum of function has not yet been outlined, recent discoveries have revealed the emerging roles of α-N-terminal methylation in protein-chromatin interactions, DNA damage repair, and chromosome segregation. Herein, an overview of the discovery of protein N-terminal methyltransferases and functions of α-N-terminal methylation is presented. In addition, substrate recognition, mechanisms, and inhibition of N-terminal methyltransferases are reviewed. Opportunities and gaps in protein α-N-terminal methylation are also discussed.

Keywords: enzymes; inhibitors; methylation; proteins; reaction mechanisms.