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

Rune Hartmann, G Walko, J Justesen

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)54-58
Number of pages5
JournalFEBS Letters
Volume507
Issue number1
DOIs
Publication statusPublished - 19 Oct 2001

Keywords

  • 2',5'-Oligoadenylate Synthetase/antagonists & inhibitors
  • Animals
  • Cations, Divalent/pharmacology
  • Enzyme Inhibitors/pharmacology
  • Humans
  • In Vitro Techniques
  • Isoenzymes/antagonists & inhibitors
  • Kinetics
  • Protein Structure, Quaternary
  • Recombinant Proteins/chemistry
  • Zinc/pharmacology

Fingerprint Dive into the research topics of 'Inhibition of 2'-5' oligoadenylate synthetase by divalent metal ions'. Together they form a unique fingerprint.

Cite this