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. 2022 Apr 12;50(8):4216–4245. doi: 10.1093/nar/gkac224

Table 1.

Overview of MTase classification

Name Structure Exemplary crystal structure
Class I Rossmann-Fold MTases (264,286–288) Seven β-sheets flanked by three α-helices on each side forming an αβα-sandwich nsp10-nsp16 methyltransferase complex SARS-CoV-2 PDB 6YZ1 (264)
ClassII(21) Eight central β-sheets framed by several α-helices at both ends including a characteristic central, antiparallel β-sheet MetH methionine synthase E. coli K12 PDB 1MSK (21)
Class III (22) Two αβ-clusters each containing five central β-sheets surrounded by four α-helices CbiF cobalt-precorrin-4 transmethylase Priestia megaterium PDB 1CBF (22)
Class IV SPOUT (SpoU-TrmD) MTases (26,289) Characteristic knot structure at the C terminus; six-stranded parallel β-sheet surrounded by seven α-helices RlmB 2′-O-methyltransferase E. coli PDB: 1GZ0 (289)
Class V SET-domain containing proteins (23,290) Combination of three β-sheet formations each consisting of three β-strands surrounding the remarkable ‘pseudoknot’ at the C terminus SET7/9 lysine methyltransferase H. sapiens PDB: 1MT6 (23)
Class VI Transmembrane MTases (291,292) Five transmembrane α-helices and a cofactor-binding pocket enclosed within a highly conserved C-terminal catalytic subdomain comprising an α-helix. Isoprenylcysteine carboxyl methyltransferase (ICMT), Methanosarcina acetivorans PDB: 4A2N (291)
ClassVII TIM barrel MTases (293,294) Partial (α/β)6 TIM barrel or full TIM barrel in some cases: a β-sheet is anchored inside by peripheral α-helices, on top the [4Fe-4S] cluster. MiaB radical methylthiotransferase Bacteroides uniformis PDB: 7MJV (294)
ClassVIII(295,296) Six-stranded anti-parallel β-barrel, β-sheets are connected by numerous extended loops. TrmO/YaeB tRNA methyltransferase Archaeoglobus fulgidus PDB: 2NV4 (295,296)
Class IX (297) Two four-stranded antiparallel β-sheets forming a concave surface with five α-helices at the reverse side of the protein. SsTaw3 tRNA-yW N-4 Methyltransferases Saccharolobus solfataricus PDB: 1TLJ (297)

The table includes information about characteristic structural features and examples of enzyme structures.