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

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 Hg2+ strongly inhibits the function of HRI (IC50 = 0.6 μM), and nitric oxide fully reverses this inhibition. Other divalent metal cations, such as Fe2+, Cu2+, Cd2+, Zn2+ and Pb2+, also significantly inhibit kinase activity with IC50 values of 1.9-8.5 μM. Notably, inhibition by cations other than Hg2+ is not reversed by nitric oxide. Our present data support dual roles of Hg2+ and nitric oxide in the regulation of protein synthesis during cell emergency states.