Specificity of the Metalloregulator CueR for Monovalent Metal Ions: Possible Functional Role of a Coordinated Thiol?

Dániel Szunyogh, Hajnalka Szokolai, Peter W. Thulstrup, Flemming H. Larsen, Béla Gyurcsik, Niels Johan Christensen, Monika Stachura, Lars Hemmingsen, Attila Jancsõ

Research output: Contribution to journalArticle

9 Citations (Scopus)


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 AgI, ZnII, and HgII binding to model systems encompassing the metal-ion-binding loop of CueR from E. coli and V. cholerae. In the presence of AgI, a conserved cysteine residue displays a pKa 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 Ser 77 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.

Original languageEnglish
Pages (from-to)15756-15761
Number of pages6
JournalAngewandte Chemie - International Edition
Issue number52
Publication statusPublished - Dec 21 2015



  • metal-sensor proteins
  • metal-site structure
  • molecular modeling
  • peptides
  • thiol coordination

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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