Inhibition of 2 '-5 ' oligoadenylate synthetase by divalent metal ions

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 p 69 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 manganes e ions were without effect. However, manganese ions can replace magnesium i ons as activator. The inhibitory effect of zinc ions was characterised in d etail. The inhibitory constants of Zn2+ were estimated to be 0.10 mM for OA S1p42 and to 0.02 mM for OAS2p69. Cross-linking experiments showed that zin c ions can control the oligomerisation by enhancing the formation of tetram eric forms of OAS1p42 (C) 2001 Federation of European Biochemical Societies . Published by Elsevier Science B.V.. All rights reserved.