Structural highlights
Function
[LCMT1_YEAST] Methylates the carboxyl group of the C-terminal leucine residue of protein phosphatase 2A catalytic subunits to form alpha-leucine ester residues. Acts on the two major protein phosphatase 2A catalytic subunits, PPH21 and PPH22.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The important role of the serine/threonine protein phosphatase 2A (PP2A) in various cellular processes requires a precise and dynamic regulation of PP2A activity, localization, and substrate specificity. The regulation of the function of PP2A involves the reversible methylation of the COOH group of the C-terminal leucine of the catalytic subunit, which, in turn, controls the enzyme's heteromultimeric composition and confers different protein recognition and substrate specificity. We have determined the structure of PPM1, the yeast methyltransferase responsible for methylation of PP2A. The structure of PPM1 reveals a common S-adenosyl-l-methionine-dependent methyltransferase fold, with several insertions conferring the specific function and substrate recognition. The complexes with the S-adenosyl-l-methionine methyl donor and the S-adenosyl-l-homocysteine product and inhibitor unambiguously revealed the co-substrate binding site and provided a convincing hypothesis for the PP2A C-terminal peptide binding site. The structure of PPM1 in a second crystal form provides clues to the dynamic nature of the PPM1/PP2A interaction.
Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl methyltransferase involved in the regulation of protein phosphatase 2A activity.,Leulliot N, Quevillon-Cheruel S, Sorel I, de La Sierra-Gallay IL, Collinet B, Graille M, Blondeau K, Bettache N, Poupon A, Janin J, van Tilbeurgh H J Biol Chem. 2004 Feb 27;279(9):8351-8. Epub 2003 Dec 4. PMID:14660564[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wu J, Tolstykh T, Lee J, Boyd K, Stock JB, Broach JR. Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatory subunits in vivo. EMBO J. 2000 Nov 1;19(21):5672-81. PMID:11060018 doi:http://dx.doi.org/10.1093/emboj/19.21.5672
- ↑ Kalhor HR, Luk K, Ramos A, Zobel-Thropp P, Clarke S. 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. 2001 Nov 15;395(2):239-45. PMID:11697862 doi:http://dx.doi.org/10.1006/abbi.2001.2558
- ↑ Leulliot N, Quevillon-Cheruel S, Sorel I, de La Sierra-Gallay IL, Collinet B, Graille M, Blondeau K, Bettache N, Poupon A, Janin J, van Tilbeurgh H. Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl methyltransferase involved in the regulation of protein phosphatase 2A activity. J Biol Chem. 2004 Feb 27;279(9):8351-8. Epub 2003 Dec 4. PMID:14660564 doi:http://dx.doi.org/10.1074/jbc.M311484200
