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Abstract
| Metal-ion-responsive transcriptional regulators within the MerR family effectively discriminate between mono- and divalent metal ions.Herein we address the origin of the specificity of the CueR protein for monovalent metal ions.Several spectroscopic techniques were employed to study $Ag^I$ ,$Zn^{II}$ ,and $Hg^{II}$ binding to model systems encompassing the metal-ion-binding loop of CueR from E. coli and V. cholerae. In the presence of $Ag^I$ ,a conserved cysteine residue displays a $pK_a$ value for deprotonation of the thiol that is close to the physiological pH value.This property is only observed with the monovalent metal ion. Quantum chemically optimized structures of the CueR metal site with Cys 112 protonated demonstrate that the conserved Ser77 backbone carbonyl oxygen atom from the other monomer of the homodimer is “pulled” towards the metal site.A common allosteric mechanism of the metalloregulatory members of the MerR family is proposed. For CueR, the mechanism relies on the protonation of Cys 112. |