DNA cytosine methylation: structural and thermodynamic characterization of the epigenetic marking mechanism.

ABSTRACT: DNA cytosine methyltransferases regulate the expression of the genome through the precise epigenetic marking of certain cytosines with a methyl group, and aberrant methylation is a hallmark of human diseases including cancer. Targeting these enzymes for drug design is currently a high priority. We have utilized ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations to investigate extensively the reaction mechanism of the representative DNA methyltransferase HhaI (M.HhaI) from prokaryotes, whose overall mechanism is shared with the mammalian enzymes. We obtain for the first time full free energy profiles for the complete reaction, together with reaction dynamics in atomistic detail. Our results show an energetically preferred mechanism in which nucleop

SUBMITTER: Yang J 

PROVIDER: S-EPMC3687104 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature