8AJP

Crystal structure of Halogen methyl transferase from Paraburkholderia xenovorans at 1.8 A in complex with SAH

8AJP の概要

• エントリーDOI: 10.2210/pdb8ajp/pdb
• 分子名称: Halide methyl transferase, S-ADENOSYL-L-HOMOCYSTEINE, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: methyltransferase, sah complex, halide methyl transferase, sam regeneration, biocatalysis, s-adenosylmethionine, late stage methylation, transferase
• 由来する生物種: Paraburkholderia xenovorans
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23291.50

構造登録者

Leisinger, F.,Seebeck, F.P. (登録日: 2022-07-28, 公開日: 2022-08-31, 最終更新日: 2025-12-10)

主引用文献

Wen, X.,Leisinger, F.,Leopold, V.,Seebeck, F.P.
Synthetic Reagents for Enzyme-Catalyzed Methylation.
Angew.Chem.Int.Ed.Engl., 61:e202208746-e202208746, 2022

PubMed Abstract: Late-stage methylation is a key technology in the development of pharmaceutical compounds. Methyltransferase biocatalysis may provide powerful options to insert methyl groups into complex molecules with high regio- and chemoselectivity. The challenge of a large-scale application of methyltransferases is their dependence on S-adenosylmethionine (SAM) as a stoichiometric, and thus exceedingly expensive co-substrate. As a solution to this problem, we and others have explored the use of methyl halides as reagents for the in situ regeneration of SAM. However, the need to handle volatile electrophiles, such as methyl iodide (MeI), may also hamper applications at scale. As a more practical solution, we have now developed an enzyme-catalyzed process for the regeneration of SAM with methyl toluene sulfonate. Herein, we describe enzymes from the thiopurine methyltransferase family that accept sulfate- and sulfonate-based methyl donors to convert S-adenosylhomocysteine into SAM with efficiencies that rival MeI-based reactions.

PubMed: 35989225
DOI: 10.1002/anie.202208746

実験手法

X-RAY DIFFRACTION (1.8 Å)