How do SET-domain protein lysine methyltransferases achieve the methylation state specificity? Revisited by Ab initio QM/MM molecular dynamics simulations.

ABSTRACT: A distinct protein lysine methyltransferase (PKMT) only transfers a certain number of methyl group(s) to its target lysine residue in spite of the fact that a lysine residue can be either mono-, di-, or tri-methylated. In order to elucidate how such a remarkable product specificity is achieved, we have carried out ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations on two SET-domain PKMTs: SET7/9 and Rubisco large subunit methyltransferase (LSMT). The results indicate that the methylation state specificity is mainly controlled by the methyl-transfer reaction step, and confirm that SET7/9 is a mono-methyltransferase while LSMT has both mono-and di-methylation activities. It is found that the binding of the methylated lysine substrate in the active site o

SUBMITTER: Hu P 

PROVIDER: S-EPMC2639776 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature