Inhibition of 2′‐5′ oligoadenylate synthetase by divalent metal ions

FEBS Letters

Justesen, Just¹  Walko, Gernot¹  Hartmann, Rune¹ 

[1] Department of Molecular and Structural Biology, University of Aarhus, C.F. Møllers alle, Bygn. 130, DK-8000 Aarhus C, Denmark

关键词: Oligoadenylate synthetase;    Divalent metal ions;    Inhibition;   

DOI  :  10.1016/S0014-5793(01)02918-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Zn²⁺ 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

【 授权许可】

Unknown