Details

Autor(en) / Beteiligte

• Cornelissen, Nicolas V
• Michailidou, Freideriki
• Muttach, Fabian
• Rau, Kristina
• Rentmeister, Andrea

Titel

Nucleoside-modified AdoMet analogues for differential methyltransferase targeting

Ist Teil von

• Chemical communications (Cambridge, England), 2020-02, Vol.56 (14), p.2115-2118

Ort / Verlag

England: Royal Society of Chemistry

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Methyltransferases (MTases) modify a wide range of biomolecules using S -adenosyl- l -methionine (AdoMet) as the cosubstrate. Synthetic AdoMet analogues are powerful tools to site-specifically introduce a variety of functional groups and exhibit potential to be converted only by distinct MTases. Extending the size of the substituent at the sulfur/selenium atom provides selectivity among MTases but is insufficient to discriminate between promiscuous MTases. We present a panel of AdoMet analogues differing in the nucleoside moiety (NM-AdoMets). These NM-AdoMets were efficiently produced by a previously uncharacterized methionine adenosyltransferase (MAT) from methionine and ATP analogues, such as ITP and N 6 -propargyl-ATP. The N 6 -modification changed the relative activity of three representative MTases up to 13-fold resulting in discrimination of substrates for the methyl transfer and could also be combined with transfer of allyl and propargyl groups. Methyltransferases modify a wide range of biomolecules using S -adenosyl- l -methionine (AdoMet) as cosubstrate. Enzymatic generation of nucleoside-modified AdoMet analogues and conversion by different methyltransferases is shown.