Interaction of DNA Methyltransferase Dnmt3a with Phosphorus Analogs of S-Adenosylmethionine and S-Adenosylhomocysteine

• DOI: 10.1134/s0026893323040064
• Publication Date: 2023-08-08T18:01:58Z
• Authors: V. L. Filonov; M. A. Khomutov; A. V. Sergeev; A. L. Khandazhins...; S. N. Kochetkov; E. S. Gromova; A. R. Khomutov
• Keywords: DNA methyltransferase; Cytosine; CpG site; Transferase; Methyl group

Abstract Enzymatic methyltransferase reactions are of crucial importance for cell metabolism. S -Adenosyl- L -methionine (AdoMet) is a main donor the methyl group. DNA, RNA, proteins, and low-molecular-weight compounds substrates methyltransferases. In mammals, DNA Dnmt3a de novo methylates C5 position cytosine residues in CpG sequences DNA. The methylation pattern one factors that determine epigenetic regulation gene expression. Here, interactions with catalytic domain was first time studied phosphonous phosphonic analogs AdoMet -adenosyl- -homocysteine (AdoHcy), which carboxyl group substituted respective phosphorus-containing These were shown to be Dnmt3a, efficiency only halved as compared natural AdoMet. Both AdoHcy, inhibitor, showed similar inhibitory activities toward approximately four times less active than AdoHcy. finding activity quite unexpected because geometry charge their groups differ substantially. AdoHcy discussed promising tools investigation