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Specificity of the Metalloregulator CueR for Monovalent Metal Ions: Possible Functional Role of a Coordinated Thiol?
Author(s) -
Szunyogh Dániel,
Szokolai Hajnalka,
Thulstrup Peter W.,
Larsen Flemming H.,
Gyurcsik Béla,
Christensen Niels Johan,
Stachura Monika,
Hemmingsen Lars,
Jancsó Attila
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201508555
Subject(s) - protonation , chemistry , deprotonation , metal , metal ions in aqueous solution , cysteine , allosteric regulation , stereochemistry , crystallography , ion , biochemistry , enzyme , organic chemistry
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 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.