TY - JOUR
T1 - Specificity of the metalloregulator CueR for monovalent metal ions
T2 - possible functional role of a coordinated thiol?
AU - Szunyogh, Dániel
AU - Szokolai, Hajnalka
AU - Thulstrup, Peter Waaben
AU - Larsen, Flemming Hofmann
AU - Gyurcsik, Béla
AU - Christensen, Niels Johan
AU - Stachura, Monika Kinga
AU - Hemmingsen, Lars Bo Stegeager
AU - Jancsó, Attila
N1 - © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/12/21
Y1 - 2015/12/21
N2 - 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.
AB - 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.
U2 - 10.1002/anie.201508555
DO - 10.1002/anie.201508555
M3 - Journal article
C2 - 26563985
SN - 1433-7851
VL - 54
SP - 15756
EP - 15761
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
IS - 52
ER -