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Eukaryotic initiation factor 2α kinase is a nitric oxide‐responsive mercury sensor enzyme: Potent inhibition of catalysis by the mercury cation and reversal by nitric oxide
Author(s) -
Martinkova Marketa,
Igarashi Jotaro,
Shimizu Toru
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.07.055
Subject(s) - nitric oxide , chemistry , heme , kinase , divalent , biochemistry , enzyme , nitrosylation , biophysics , biology , organic chemistry
The activity of one of the eukaryotic initiation factor 2α kinases, heme‐regulated inhibitor (HRI), is modulated by heme binding. Here, we demonstrate for the first time that Hg 2+ strongly inhibits the function of HRI (IC 50 = 0.6 μM), and nitric oxide fully reverses this inhibition. Other divalent metal cations, such as Fe 2+ , Cu 2+ , Cd 2+ , Zn 2+ and Pb 2+ , also significantly inhibit kinase activity with IC 50 values of 1.9–8.5 μM. Notably, inhibition by cations other than Hg 2+ is not reversed by nitric oxide. Our present data support dual roles of Hg 2+ and nitric oxide in the regulation of protein synthesis during cell emergency states.