Hauptseite > Publikationsdatenbank > Enzymatic C3-Methylation of Indoles Using Methyltransferase PsmD─Crystal Structure, Catalytic Mechanism, and Preparative Applications > print |
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024 | 7 | _ | |a 10.1021/acscatal.2c04240 |2 doi |
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100 | 1 | _ | |a Amariei, Diana A. |0 P:(DE-Juel1)185993 |b 0 |
245 | _ | _ | |a Enzymatic C3-Methylation of Indoles Using Methyltransferase PsmD─Crystal Structure, Catalytic Mechanism, and Preparative Applications |
260 | _ | _ | |a Washington, DC |c 2022 |b ACS |
336 | 7 | _ | |a article |2 DRIVER |
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520 | _ | _ | |a Enantioselective methylation is a challenging task in organic chemistry, yet often desirable in drug discovery and optimization. S-Adenosyl methionine (SAM)-dependent methyltransferases (MTases) offer a selective alternative to chemical synthesis and an abundance of potential scaffolds. The crystal structure of C3-indole MTase PsmD from Streptomyces griseofuscus, involved in the biosynthesis of the acetylcholinesterase inhibitor physostigmine, was determined via X-ray crystallography. The amino acid residues essential for catalysis were identified by site-directed mutagenesis, and a mechanism of action was proposed. Furthermore, a PsmD ortholog was identified and characterized. The variant catalyzed enantioselective C-methylation over a broad substrate scope while displaying increased stability. Using this enzyme, preparative-scale enzymatic methylation was performed in cell-free extracts in combination with an SAM recycling system, eliminating the need for cofactor supplementation. |
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700 | 1 | _ | |a David, Benoit |0 P:(DE-Juel1)190107 |b 2 |
700 | 1 | _ | |a Schneider, Pascal |0 P:(DE-Juel1)176354 |b 3 |
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700 | 1 | _ | |a Weiergräber, Oliver H. |0 P:(DE-Juel1)131988 |b 6 |
700 | 1 | _ | |a Pietruszka, Jörg |0 P:(DE-Juel1)128906 |b 7 |e Corresponding author |
773 | _ | _ | |a 10.1021/acscatal.2c04240 |g p. 14130 - 14139 |0 PERI:(DE-600)2584887-2 |n 22 |p 14130 - 14139 |t ACS catalysis |v 12 |y 2022 |x 2155-5435 |
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