8RXG
Crystal structure of alpha-keto C-methyl transferase SgvM bound to SAM
Summary for 8RXG
| Entry DOI | 10.2210/pdb8rxg/pdb |
| Descriptor | Methyltransferase, ZINC ION, 2-OXO-4-METHYLPENTANOIC ACID, ... (6 entities in total) |
| Functional Keywords | s adenosylmethionine-dependent methyltransferases, biocatalysis, c-alkylation, transferase |
| Biological source | Streptomyces griseoviridis |
| Total number of polymer chains | 1 |
| Total formula weight | 37540.92 |
| Authors | Gerhardt, S.,Andexer, J.N. (deposition date: 2024-02-07, release date: 2024-07-24, Last modification date: 2024-10-16) |
| Primary citation | Sommer-Kamann, C.,Breiltgens, J.,Zou, Z.,Gerhardt, S.,Saleem-Batcha, R.,Kemper, F.,Einsle, O.,Andexer, J.N.,Muller, M. Structures and Protein Engineering of the alpha-Keto Acid C-Methyltransferases SgvM and MrsA for Rational Substrate Transfer. Chembiochem, 25:e202400258-e202400258, 2024 Cited by PubMed Abstract: S-adenosyl-l-methionine-dependent methyltransferases (MTs) are involved in the C-methylation of a variety of natural products. The MTs SgvM from Streptomyces griseoviridis and MrsA from Pseudomonas syringae pv. syringae catalyze the methylation of the β-carbon atom of α-keto acids in the biosynthesis of the antibiotic natural products viridogrisein and 3-methylarginine, respectively. MrsA shows high substrate selectivity for 5-guanidino-2-oxovalerate, while other α-keto acids, such as the SgvM substrates 4-methyl-2-oxovalerate, 2-oxovalerate, and phenylpyruvate, are not accepted. Here we report the crystal structures of SgvM and MrsA in the apo form and bound with substrate or S-adenosyl-l-methionine. By investigating key residues for substrate recognition in the active sites of both enzymes and engineering MrsA by site-directed mutagenesis, the substrate range of MrsA was extended to accept α-keto acid substrates of SgvM with uncharged and lipophilic β-residues. Our results showcase the transfer of the substrate scope of α-keto acid MTs from different biosynthetic pathways by rational design. PubMed: 38887142DOI: 10.1002/cbic.202400258 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.813 Å) |
Structure validation
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