8AJP

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

Summary for 8AJP

• Entry DOI: 10.2210/pdb8ajp/pdb
• Descriptor: Halide methyl transferase, S-ADENOSYL-L-HOMOCYSTEINE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: methyltransferase, sah complex, halide methyl transferase, sam regeneration, biocatalysis, s-adenosylmethionine, late stage methylation, transferase
• Biological source: Paraburkholderia xenovorans
• Total number of polymer chains: 1
• Total formula weight: 23291.50

Authors

Leisinger, F.,Seebeck, F.P. (deposition date: 2022-07-28, release date: 2022-08-31, Last modification date: 2024-01-31)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)