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.