InterPro domain: IPR007213

This entry includes a group of methyltransferases such as leucine carboxyl methyltransferase 1 (known as Ppm1 in yeast and LCMT1 in mammals), leucine carboxyl methyltransferase 2 (Ppm2/LCMT2) and O-methyltransferase TcmP.

Ppm1 regulates the activity of serine/threonine phosphatase 2A (PP2A) through methylation of the C-terminal leucine residue of the catalytic subunit of PP2A [ 1 , 2 , 3 ]. This affects the heteromultimeric composition of PP2A which in turn affects protein recognition and substrate specificity. Like many other methyltransferases Ppm1 uses S-adenosylmethionine (SAM) as the methyl donor. Ppm1 contains the common SAM-dependent methyltransferase core fold, with various insertions and additions creating a specific PP2A binding site [ 4 ]. Ppm2, a homologue of Ppm1, is a S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway, which is part of tRNA modification [ 5 ].

Streptomyces glaucescens TcmP is an O-methyltransferase that catalyses the methylation of the C-9 carboxy group of tetracenomycin E (TCM E) to yield TCM A2, which is then further processed to produce the antibiotic TCM C [ 6 ].

1. Purification of porcine brain protein phosphatase 2A leucine carboxyl methyltransferase and cloning of the human homologue. Biochemistry 38, 16539-47
2. Protein phosphatase methyltransferase 1 (Ppm1p) is the sole activity responsible for modification of the major forms of protein phosphatase 2A in yeast. Arch. Biochem. Biophys. 395, 239-45
3. Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatory subunits in vivo. EMBO J. 19, 5672-81
4. Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl methyltransferase involved in the regulation of protein phosphatase 2A activity. J. Biol. Chem. 279, 8351-8
5. Biosynthesis of wybutosine, a hyper-modified nucleoside in eukaryotic phenylalanine tRNA. EMBO J. 25, 2142-54
6. Triple hydroxylation of tetracenomycin A2 to tetracenomycin C involving two molecules of O(2) and one molecule of H(2)O. Org. Lett. 2, 3225-7