InterPro domain: IPR013217

Methyl transfer from the ubiquitous donor S-adenosyl-L-methionine (SAM) to either nitrogen, oxygen or carbon atoms is frequently employed in diverse organisms ranging from bacteria to plants and mammals. The reaction is catalyzed by methyltransferases (Mtases) and modifies DNA, RNA, proteins and small molecules, such as catechol for regulatory purposes. The various aspects of the role of DNA methylation in prokaryotic restriction-modification systems and in a number of cellular processes in eukaryotes including gene regulation and differentiation is well documented.

This entry represents a methyltransferase domain found in a large variety of SAM-dependent methyltransferases including, but not limited to:

• Hexaprenyldihydroxybenzoate methyltransferase ( 2.1.1.114 ), a mitochodrial enzyme involved in ubiquinone biosynthesis [ 1 ]
• Fatty acid synthase ( 2.3.1.85 ), a biosynthetic enzyme catalysing the formation of long-chain fatty acids
• Glycine N-methyltransferase ( 2.1.1.20 ) which catalyses the SAM-dependent methylation of glycine to form sarcosine and may play a role in regulating the methylation potential of the cell [ 2 ]
• Enniatin synthetase, involved in non-ribosomal biosynthesis of cyclohexadepsipeptidase, enniatin [ 3 ]
• Histamine N-methyltransferase ( 2.1.1.8 ), a SAM-dependent histamine-inactivating enzyme [ 4 ]
• A probable cobalt-precorrin-6Y C(15)-methyltransferase thought to be involved in adenosylcobalamin biosynthesis [ 5 ]
• A polyketide synthase, important for the synthesis of chaetoviridin A and chaetomugilin A in the fungus Chaetomium [ 6 ].

Structural studies show that this domain forms the Rossman-like alpha-beta fold typical of SAM-dependent methyltransferases [ 7 , 8 , 9 ].

1. Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis. J. Biol. Chem. 274, 21665-72
2. Mammalian glycine N-methyltransferases. Comparative kinetic and structural properties of the enzymes from human, rat, rabbit and pig livers. Comp. Biochem. Physiol., B 106, 601-11
3. Mutational analysis of the N-methyltransferase domain of the multifunctional enzyme enniatin synthetase. J. Biol. Chem. 275, 30826-32
4. Guinea pig histamine N-methyltransferase: cDNA cloning and mRNA distribution. Jpn. J. Pharmacol. 85, 105-8
5. Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium. J. Bacteriol. 175, 3303-16
6. Biochemical and Structural Basis for Controlling Chemical Modularity in Fungal Polyketide Biosynthesis. J. Am. Chem. Soc. 137, 9885-93
7. Crystal structure of YecO from Haemophilus influenzae (HI0319) reveals a methyltransferase fold and a bound S-adenosylhomocysteine. Proteins 45, 397-407
8. Crystal structure of glycine N-methyltransferase from rat liver. Biochemistry 35, 11985-93
9. Glycine N-methyltransferases: a comparison of the crystal structures and kinetic properties of recombinant human, mouse and rat enzymes. Proteins 57, 331-7