How to Tell an N from an O: Controlling the Chemoselectivity of Methyltransferases.

ABSTRACT: S-Adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) are important enzymes in numerous biological pathways. They share a common S _N 2 mechanism but act on different nucleophilic substrates in vivo. Therefore, MTs have a specific chemoselectivity to transfer CH₃ onto the correct atom type and substrate. Caffeate O-MT from Prunus persica (PpCaOMT) and anthranilate N-MT from Ruta graveolens (RgANMT) share a high similarity regarding their amino acid sequence (>74%). Nevertheless, the physiological substrates (caffeate vs anthranilate) and attacking nucleophiles (hydroxyl vs amino group) are strikingly different. We demonstrate that the differing chemoselectivity is governed by different conformational st

SUBMITTER: Jockmann E 

PROVIDER: S-EPMC12013660 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature