YDR435c: PPM1 methyltransferase

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Structure of the PPM1 methyltransferase. A, topology diagram of the PPM1 methyltransferase (31). The different domains not belonging to the core methyltransferase fold are boxed. The plane of the core beta-sheet is perpendicular to the plane of the figure, and the core alpha-helices are roughly parallel to the strands of the beta-sheet. The binding site for AdoMet (or AdoHCys) and the putative binding site for the C-terminal peptide of PP2A are indicated. The secondary structure elements are color-coded as follows: blue, core MT domain; pink, region I; red, region II; green, region III; and orange, region IV. B and C, stereo ribbon representation of the structure of PPM1 in crystal form I bound to AdoMet (stick). The same color code as in panel A is used. Only some of the secondary structure elements are labeled for clarity. No significant conformational rearrangements are observed between the AdoMet, AdoHCys, or apoprotein structures. In crystal form II, the alpha helix of region III could not be seen in the electron density map and is missing from the model. Structure views are generated using PyMol (pymol.sourceforge.net/). The view in panel C is 90° rotated compared with that in panel B. Nter, N terminus; Cter, C terminus.
Function PPM1: carboxy methyl transferase for protein phosphatase 2A catalytic subunit
Fold SAM-dependent methyl transferase fold
Resolution 1.8
Remarks Free form and complexes with SAM and AdoHCy
PDB code 1RJD
Reference N. Leulliot, S. Quevillon-Cheruel, I. Sorel, I.L. de La Sierra-Gallay, B. Collinet, M. Graille, K. Blondeau, N. Bettache, A. Poupon, J. Janin and H. Van Tilbeurgh, J. Biol. Chem. 279 (2004), pp. 8351-8358. Full text

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.