8QNO

Crystal structure of S-adenosyl-L-homocysteine hydrolase treated at 368 K from Pyrococcus furiosus in complex with inosine

Summary for 8QNO

• Entry DOI: 10.2210/pdb8qno/pdb
• Related: 7R37 7R38 7R39 7R3A 8COD
• Descriptor: Adenosylhomocysteinase, INOSINE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: complex, s-adenosyl-l-homocysteine (sah), s-adenosyl-l-methionine (sam), hydrolase
• Biological source: Pyrococcus furiosus
• Total number of polymer chains: 2
• Total formula weight: 101103.82

Authors

Saleem-Batcha, R.,Koeppl, L.H.,Popadic, D.,Andexer, J.N. (deposition date: 2023-09-27, release date: 2024-08-21, Last modification date: 2024-11-13)

Primary citation

Koeppl, L.H.,Popadic, D.,Saleem-Batcha, R.,Germer, P.,Andexer, J.N.
Structure, function and substrate preferences of archaeal S-adenosyl-L-homocysteine hydrolases.
Commun Biol, 7:380-380, 2024

PubMed Abstract: 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.

PubMed: 38548921
DOI: 10.1038/s42003-024-06078-9

Experimental method

X-RAY DIFFRACTION (2.033 Å)