8ovh
From Proteopedia
Crystal structure of O-acetyl-L-homoserine sulfhydrolase from Saccharomyces cerevisiae in complex with Pyridoxal-5'-phosphate
Structural highlights
FunctionCYSD_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).[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedS-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. 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[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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