Structural Basis for Control of Methylation Extent in Polyketide Synthase Metal-Dependent C-Methyltransferases.

ABSTRACT: Installation of methyl groups can significantly improve the binding of small-molecule drugs to protein targets; however, site-selective methylation often presents a significant synthetic challenge. Metal- and S-adenosyl-methionine (SAM)-dependent methyltransferases (MTs) in natural-product biosynthetic pathways are powerful enzymatic tools for selective or chemically challenging C-methylation reactions. Each of these MTs selectively catalyzes one or two methyl transfer reactions. Crystal structures and biochemical assays of the Mn²⁺-dependent monomethyltransferase from the saxitoxin biosynthetic pathway (SxtA MT) revealed the structural basis for control of methylation extent. The SxtA monomethyltransferase was converted to a dimethyltransferase by modification of the met

SUBMITTER: Lao Y 

PROVIDER: S-EPMC9462956 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature