title: Inhibition of 2'-5' oligoadenylate synthetase by divalent metal ions.
abstract: OAS1 is the small form and OAS2 is the medium form of the human interferon-induced 2'-5' oligoadenylate synthetases. The p42 isoform of OAS1 and the p69 isoform of OAS2 have been expressed in insect cells and purified to give pure, highly active 2'-5' oligoadenylate synthetase. The catalysis of 2'-5' oligoadenylate synthesis is strictly dependent on double-stranded RNA and magnesium ions. We have examined the effect of a series of divalent metal ions: copper, iron and zinc ions strongly inhibited the enzymatic activity, cobalt and nickel ions were partly inhibitory whereas calcium and manganese ions were without effect. However, manganese ions can replace magnesium ions as activator. The inhibitory effect of zinc ions was characterised in detail. The inhibitory constants of Zn(2+) were estimated to be 0.10 mM for OAS1p42 and to 0.02 mM for OAS2p69. Cross-linking experiments showed that zinc ions can control the oligomerisation by enhancing the formation of tetrameric forms of OAS1p42
authors.affiliation: Department of Molecular and Structural Biology, University of Aarhus, C.F. Møllers alle, Bygn. 130, DK-8000 C, Aarhus, Denmark.
authors.forename: R
authors.initials: R
authors.lastname: Hartmann
authors.forename: G
authors.initials: G
authors.lastname: Walko
authors.forename: J
authors.initials: J
authors.lastname: Justesen
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D007700:Kinetics; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D015032:Zinc / Q000494:pharmacology
chemical_list: D002413:Cations, Divalent; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011994:Recombinant Proteins; C000607948:OAS2 protein, human; D015088:2',5'-Oligoadenylate Synthetase; D015032:Zinc