8R4Z

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

8R4Z の概要

• エントリーDOI: 10.2210/pdb8r4z/pdb
• 分子名称: 2-ketoarginine methyltransferase, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: s adenosylmethionine-dependent methyltransferases, biocatalysis, c-alkylation, asymmetric methylation, mutagenesis, transferase
• 由来する生物種: Pseudomonas syringae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77643.70

構造登録者

Gerhardt, S.,Kemper, F.,Andexer, J.N. (登録日: 2023-11-15, 公開日: 2024-07-03, 最終更新日: 2024-10-16)

主引用文献

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 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

実験手法

X-RAY DIFFRACTION (1.54 Å)