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Angew Chem Int Ed Engl. 2015 Dec 21;54(52):15756-61. doi: 10.1002/anie.201508555. Epub 2015 Nov 13.

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

Author information

1
MTA-SZTE Bioinorganic Chemistry Research Group, Dóm tér 7, 6720 Szeged (Hungary).
2
Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720 Szeged (Hungary).
3
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark).
4
Department of Food Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C (Denmark).
5
ISOLDE-CERN, 1211 Geneva 23 (Switzerland).
6
TRIUMF, 4004 Wesbrook Mall, Vancouver, BC V6T 2A3 (Canada).
7
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark). lhe@chem.ku.dk.
8
Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720 Szeged (Hungary). jancso@chem.u-szeged.hu.

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.

KEYWORDS:

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

PMID:
26563985
DOI:
10.1002/anie.201508555

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