title: Specificity of the Metalloregulator CueR for Monovalent Metal Ions: Possible Functional Role of a Coordinated Thiol?
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 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.
authors.affiliation: MTA-SZTE Bioinorganic Chemistry Research Group, Dóm tér 7, 6720 Szeged (Hungary).
authors.forename: Dániel
authors.initials: D
authors.lastname: Szunyogh
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720 Szeged (Hungary).
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Szokolai
authors.affiliation: Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark).
authors.forename: Peter W
authors.initials: PW
authors.lastname: Thulstrup
authors.affiliation: Department of Food Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C (Denmark).
authors.forename: Flemming H
authors.initials: FH
authors.lastname: Larsen
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720 Szeged (Hungary).
authors.forename: Béla
authors.initials: B
authors.lastname: Gyurcsik
authors.affiliation: Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark).
authors.forename: Niels Johan
authors.initials: NJ
authors.lastname: Christensen
authors.affiliation: ISOLDE-CERN, 1211 Geneva 23 (Switzerland).|TRIUMF, 4004 Wesbrook Mall, Vancouver, BC V6T 2A3 (Canada).
authors.forename: Monika
authors.initials: M
authors.lastname: Stachura
authors.affiliation: Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark). lhe@chem.ku.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Hemmingsen
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720 Szeged (Hungary). jancso@chem.u-szeged.hu.
authors.forename: Attila
authors.initials: A
authors.lastname: Jancsó
keywords: metal-sensor proteins; metal-site structure; molecular modeling; peptides; thiol coordination