Classification Of Prokaryotic DNA Methyltransferases By Topology And Sequence Similarity

Prokaryotic DNA methyltransferases (MTases) are essential enzymes that play a crucial role in restriction-modification systems, preventing the degradation of self DNA by restriction enzymes. In addition, they contribute to the regulation of gene expression, DNA repair, DNA replication, and other processes. Here, we propose a novel classification of prokaryotic MTases that addresses the limitations of the previous classification scheme developed by Malone and Bujnicki. The latter classification, which grouped MTases into categories such as , {beta}, {gamma}, etc., has been in use for over 20 years. We identified six structural classes (A-F) of MTases based on the 3D topology of the catalytic domain. This was achieved by analyzing the available 3D structures and certain predicted 3D structures of MTases from the AlphaFold DB. The catalytic domains of each class of MTase exhibit homology not only in structure but also in conserved motifs. Based on this classification, we developed an algorithm for the automatic annotation of MTase genes and assignment of their structural class. Our new classification system facilitates the recovery of MTase evolution and MTase annotations in both existing and new sequence data sets. This is particularly important for understanding the complex relationships between MTases and their roles in various biological processes. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=183 SRC="FIGDIR/small/571470v6_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@4be6e3org.highwire.dtl.DTLVardef@12381dcorg.highwire.dtl.DTLVardef@22a79dorg.highwire.dtl.DTLVardef@12a62a6_HPS_FORMAT_FIGEXP M_FIG C_FIG