8R4Z

Crystal structure of alpha keto acid C-methyl-transferases MrsA native-form

Summary for 8R4Z

• Entry DOI: 10.2210/pdb8r4z/pdb
• Descriptor: 2-ketoarginine methyltransferase, MAGNESIUM ION (3 entities in total)
• Functional Keywords: s adenosylmethionine-dependent methyltransferases, biocatalysis, c-alkylation, asymmetric methylation, mutagenesis, transferase
• Biological source: Pseudomonas syringae
• Total number of polymer chains: 2
• Total formula weight: 77643.70

Authors

Gerhardt, S.,Kemper, F.,Andexer, J.N. (deposition date: 2023-11-15, release date: 2024-07-03, 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

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: 38887142
DOI: 10.1002/cbic.202400258

Experimental method

X-RAY DIFFRACTION (1.54 Å)