Homologous Superfamily

S-adenosyl-L-methionine-dependent methyltransferase (IPR029063)

Short name: SAM-dependent_MTases

Overlapping entries



This entry represents the S-adenosyl-L-methionine-dependent methyltransferase (SAM MTase) superfamily. Methyltransferases transfer a methyl group from a donor to an acceptor. SAM-binding methyltransferases utilise the ubiquitous methyl donor SAM as a cofactor to methylate proteins, small molecules, lipids, and nucleic acids. All SAM MTases contain a structurally conserved SAM-binding domain consisting of a central seven-stranded beta-sheet that is flanked by three alpha-helices per side of the sheet [PMID: 12504684].

A review published in 2003 [PMID: 12826405] divides all methyltransferases into 5 classes based on the structure of their catalytic domain (fold):

  • class I: Rossmann-like alpha/beta
  • class II: TIM beta/alpha-barrel alpha/beta
  • class III: tetrapyrrole methylase alpha/beta
  • class IV: SPOUT alpha/beta
  • class V: SET domain all beta

Another paper [PMID: 21858014] based on a study of the Saccharomyces cerevisiae methyltransferome argues for four more folds:

  • class VI: transmembrane all alpha
  • class VII: DNA/RNA-binding 3-helical bundle all alpha
  • class VIII: SSo0622-like alpha+beta
  • class IX: thymidylate synthetase alpha+beta

The vast majority of methyltransferases belong to the Rossmann-like fold (Class I) which consists in a seven-stranded beta sheet adjoined by alpha helices. The beta sheet contains a central topological switch-point resulting in a deep cleft in which SAM binds. Class I methyltransferases display two conserved positions, the first one is a GxGxG motif (or at least a GxG motif) at the end of the first beta strand which is characteristic of a nucleotide-binding site and is hence used to bind the adenosyl part of SAM, the second conserved position is an acidic residue at the end of the second beta strand that forms one hydrogen bond to each hydroxyl of the SAM ribose part. The core of these enzymes is composed by about 150 amino acids that show very strong spatial conservation [PMID: 12826405].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.