8ovh

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== Function ==
== Function ==
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[https://www.uniprot.org/uniprot/CYSD_YEAST CYSD_YEAST] Catalyzes the conversion of O-acetyl-L-homoserine (OAH) into homocysteine in the methionine biosynthesis pathway (PubMed:7765825, PubMed:4609980, PubMed:795806, PubMed:36455053, PubMed:36379252). Required to efficiently reduce toxic levels of hydrogen sulfide generated when the sulfate assimilation pathway (SAP) is active (PubMed:36455053, PubMed:36379252). Also catalyzes the conversion of O-acetylserine (OAS) into cysteine, the last step in the cysteine biosynthesis pathway (PubMed:7765825, PubMed:4609980, PubMed:795806, PubMed:36455053). However, it seems that in S.cerevisiae cysteine biosynthesis occurs exclusively through the cystathionine pathway and not via direct incorporation of sulfur into OAS (PubMed:1732168). It therefore has no metabolic role in cysteine biosynthesis and may only have a regulatory role controlling OAS levels (PubMed:12586406).<ref>PMID:36379252</ref> <ref>PMID:36455053</ref> <ref>PMID:4609980</ref> <ref>PMID:7765825</ref> <ref>PMID:795806</ref> <ref>PMID:12586406</ref> <ref>PMID:1732168</ref>
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[https://www.uniprot.org/uniprot/CYSD_YEAST CYSD_YEAST] Catalyzes the conversion of O-acetyl-L-homoserine (OAH) into homocysteine in the methionine biosynthesis pathway (PubMed:36379252, PubMed:36455053, PubMed:4609980, PubMed:7765825, PubMed:795806). Required to efficiently reduce toxic levels of hydrogen sulfide generated when the sulfate assimilation pathway (SAP) is active (PubMed:36379252, PubMed:36455053). Also catalyzes the conversion of O-acetylserine (OAS) into cysteine, the last step in the cysteine biosynthesis pathway (PubMed:36455053, PubMed:4609980, PubMed:7765825, PubMed:795806). However, it seems that in S.cerevisiae cysteine biosynthesis occurs exclusively through the cystathionine pathway and not via direct incorporation of sulfur into OAS (PubMed:1732168). It therefore has no metabolic role in cysteine biosynthesis and may only have a regulatory role controlling OAS levels (PubMed:12586406).<ref>PMID:36379252</ref> <ref>PMID:36455053</ref> <ref>PMID:4609980</ref> <ref>PMID:7765825</ref> <ref>PMID:795806</ref> <ref>PMID:12586406</ref> <ref>PMID:1732168</ref>
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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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 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. Ethylation was nearly doubled with the new four-enzyme cascade, indicating a beneficial effect of the in situ production of l-methionine analogues with ScOAHS.
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S-Adenosyl-L-homocysteine hydrolase (SAHH) reversibly cleaves S-adenosyl-L-homocysteine, the product of S-adenosyl-L-methionine-dependent methylation reactions. The conversion of S-adenosyl-L-homocysteine into adenosine and L-homocysteine plays an important role in the regulation of the methyl cycle. An alternative metabolic route for S-adenosyl-L-methionine regeneration in the extremophiles Methanocaldococcus jannaschii and Thermotoga maritima has been identified, featuring the deamination of S-adenosyl-L-homocysteine to S-inosyl-L-homocysteine. Herein, we report the structural characterisation of different archaeal SAHHs together with a biochemical analysis of various SAHHs from all three domains of life. Homologues deriving from the Euryarchaeota phylum show a higher conversion rate with S-inosyl-L-homocysteine compared to S-adenosyl-L-homocysteine. Crystal structures of SAHH originating from Pyrococcus furiosus in complex with SLH and inosine as ligands, show architectural flexibility in the active site and offer deeper insights into the binding mode of hypoxanthine-containing substrates. Altogether, the findings of our study support the understanding of an alternative metabolic route for S-adenosyl-L-methionine and offer insights into the evolutionary progression and diversification of SAHHs involved in methyl and purine salvage pathways.
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Enzymatic Synthesis of l-Methionine Analogues and Application in a Methyltransferase Catalysed Alkylation Cascade.,Mohr MKF, Saleem-Batcha R, Cornelissen NV, Andexer JN Chemistry. 2023 May 26:e202301503. doi: 10.1002/chem.202301503. PMID:37235813<ref>PMID:37235813</ref>
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Structure, function and substrate preferences of archaeal S-adenosyl-L-homocysteine hydrolases.,Koeppl LH, Popadic D, Saleem-Batcha R, Germer P, Andexer JN Commun Biol. 2024 Mar 29;7(1):380. doi: 10.1038/s42003-024-06078-9. PMID:38548921<ref>PMID:38548921</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Current revision

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

PDB ID 8ovh

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