8OVH

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

Summary for 8OVH

• Entry DOI: 10.2210/pdb8ovh/pdb
• Descriptor: Homocysteine/cysteine synthase, PYRIDOXAL-5'-PHOSPHATE, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• Functional Keywords: homocysteine/cysteine synthase, o-acetyl-l-homoserine lyase, lyase
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Total number of polymer chains: 4
• Total formula weight: 205004.24

Authors

Saleem-Batcha, R.,Andexer, J.N.,Mohr, M. (deposition date: 2023-04-26, release date: 2023-06-21, Last modification date: 2024-09-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.171 Å)