8OVH

Crystal structure of O-acetyl-L-homoserine sulfhydrolase from Saccharomyces cerevisiae in complex with Pyridoxal-5'-phosphate

8OVH の概要

• エントリーDOI: 10.2210/pdb8ovh/pdb
• 分子名称: Homocysteine/cysteine synthase, PYRIDOXAL-5'-PHOSPHATE, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: homocysteine/cysteine synthase, o-acetyl-l-homoserine lyase, lyase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 205004.24

構造登録者

Saleem-Batcha, R.,Andexer, J.N.,Mohr, M. (登録日: 2023-04-26, 公開日: 2023-06-21, 最終更新日: 2024-09-25)

主引用文献

Mohr, M.K.F.,Saleem-Batcha, R.,Cornelissen, N.V.,Andexer, J.N.
Enzymatic Synthesis of l-Methionine Analogues and Application in a Methyltransferase Catalysed Alkylation Cascade.
Chemistry, 29:e202301503-e202301503, 2023

PubMed Abstract: Chemical modification of small molecules is a key step for the development of pharmaceuticals. S-adenosyl-l-methionine (SAM) analogues are used by methyltransferases (MTs) to transfer alkyl, allyl and benzyl moieties chemo-, stereo- and regioselectively onto nucleophilic substrates, enabling an enzymatic way for specific derivatisation of a wide range of molecules. l-Methionine analogues are required for the synthesis of SAM analogues. Most of these are not commercially available. In nature, O-acetyl-l-homoserine sulfhydrolases (OAHS) catalyse the synthesis of l-methionine from O-acetyl-l-homoserine or l-homocysteine, and methyl mercaptan. Here, we investigated the substrate scope of ScOAHS from Saccharomyces cerevisiae for the production of l-methionine analogues from l-homocysteine and organic thiols. The promiscuous enzyme was used to synthesise nine different l-methionine analogues with modifications on the thioether residue up to a conversion of 75 %. ScOAHS was combined with an established MT dependent three-enzyme alkylation cascade, allowing transfer of in total seven moieties onto two MT substrates. For ethylation, conversion was nearly doubled with the new four-enzyme cascade, indicating a beneficial effect of the in situ production of l-methionine analogues with ScOAHS.

PubMed: 37235813
DOI: 10.1002/chem.202301503

実験手法

X-RAY DIFFRACTION (2.171 Å)