4ymg | pdb_00004ymg

Crystal structure of SAM-bound Podospora anserina methyltransferase PaMTH1

spinqualitylabelsall models 4ymg, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ymg is a 2 chain structure with sequence from Podospora anserina. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.899Å Ligands: MG, PG4, PO4, SAM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9HGR1_PODAS Publication Abstract from PubMed Low levels of reactive oxygen species (ROS) act as important signaling molecules but in excess they can damage biomolecules. ROS regulation is therefore of key importance. Several polyphenols in general and flavonoids in particular have the potential to generate hydroxyl radicals, the most hazardous among all ROS. However, the generation of a hydroxyl radical and subsequent ROS formation can be prevented by methylation of the hydroxyl group of the flavonoids. Omethylation is performed by Omethyltransferases, members of the Sadenosylmethionine (SAM)-dependent Omethyltransferase superfamily involved in the secondary metabolism of many species across all kingdoms. In the filamentous fungus Podospora anserina, a well-established aging model, the O-methyltransferase (PaMTH1) was reported to accumulate in total and mitochondrial protein extracts during aging. In vitro functional studies revealed flavonoids and in particular myricetin as its potential substrate. The molecular architecture of PaMTH1 and the mechanism of the methyl transfer reaction remains unknown. Here, we report the crystal structures of PaMTH1 apoenzyme, PaMTH1-SAM (co-factor) and PaMTH1-SAH (by-product) co-complexes refined to 2.0, 1.9 and 1.9 A, respectively. PaMTH1 forms a tight dimer through swapping of the Ntermini. Each monomer adopts the Rossmann-fold typical for many SAM-binding methyltransferases. Structural comparisons between different Omethyltransferases reveal a strikingly similar co-factor binding pocket but differences in the substrate binding pocket indicating specific molecular determinants required for substrate selection. Furthermore, using NMR, mass spectrometry and site-directed active-site mutagenesis, we show that PaMTH1 catalyzes the transfer of the methyl group from SAM to one hydroxyl group of the myricetin in a cation-dependent manner. Structure and Biophysical Characterization of the S-adenosylmethionine Dependent O-methyltransferase PaMTH1, a Putative Enzyme Accumulating during Senescence of Podospora anserina.,Chatterjee D, Kudlinzki D, Linhard V, Saxena K, Schieborr U, Gande SL, Wurm JP, Wohnert J, Abele R, Rogov VV, Dotsch V, Osiewacz HD, Sreeramulu S, Schwalbe H J Biol Chem. 2015 May 15. pii: jbc.M115.660829. PMID:25979334 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also SAM-dependent methyltrasferase 3D structures

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