Structural highlights
Function
R9UTR3_STRGD
Publication Abstract from PubMed
Sâadenosyl-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 beta-carbon atom of alpha-keto acids in the biosynthesis of the antibiotic natural products viridogrisein and 3âmethylarginine, respectively. MrsA shows high substrate selectivity for 5âguanidino-2-oxovalerate, while other alpha-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 bound with substrate or Sâadenosyl-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 alphaâketo acid substrates of SgvM with uncharged and lipophilic betaâresidues. Our results showcase the transfer of the substrate scope of alpha-keto acid MTs from different biosynthetic pathways by rational design.
Structures and protein engineering of the alpha-keto acid C-methyltransferases SgvM and MrsA for rational substrate transfer.,Sommer-Kamann C, Breiltgens J, Zou Z, Gerhardt S, Saleem-Batcha R, Kemper F, Einsle O, Andexer JN, Muller M Chembiochem. 2024 Jun 18:e202400258. doi: 10.1002/cbic.202400258. PMID:38887142[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sommer-Kamann C, Breiltgens J, Zou Z, Gerhardt S, Saleem-Batcha R, Kemper F, Einsle O, Andexer JN, Müller M. Structures and protein engineering of the α-keto acid C-methyltransferases SgvM and MrsA for rational substrate transfer. Chembiochem. 2024 Jun 18:e202400258. PMID:38887142 doi:10.1002/cbic.202400258
