Specificity of the metalloregulator CueR for monovalent metal ions: possible functional role of a coordinated thiol?

Dániel Szunyogh; Hajnalka Szokolai; Peter Waaben Thulstrup; Flemming Hofmann Larsen; Béla Gyurcsik; Niels Johan Christensen; Monika Kinga Stachura; Lars Bo Stegeager Hemmingsen; Attila Jancsó

doi:10.1002/anie.201508555

Specificity of the metalloregulator CueR for monovalent metal ions: possible functional role of a coordinated thiol?

Dániel Szunyogh, Hajnalka Szokolai, Peter Waaben Thulstrup, Flemming Hofmann Larsen, Béla Gyurcsik, Niels Johan Christensen, Monika Kinga Stachura, Lars Bo Stegeager Hemmingsen, Attila Jancsó

12 Citations (Scopus)

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.

Original language	English
Journal	Angewandte Chemie International Edition
Volume	54
Issue number	52
Pages (from-to)	15756-15761
Number of pages	6
ISSN	1433-7851
DOIs	https://doi.org/10.1002/anie.201508555
Publication status	Published - 21 Dec 2015

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Szunyogh, D., Szokolai, H., Thulstrup, P. W., Larsen, F. H., Gyurcsik, B., Christensen, N. J., Stachura, M. K., Hemmingsen, L. B. S., & Jancsó, A. (2015). Specificity of the metalloregulator CueR for monovalent metal ions: possible functional role of a coordinated thiol? Angewandte Chemie International Edition, 54(52), 15756-15761. https://doi.org/10.1002/anie.201508555

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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.",

author = "D{\'a}niel Szunyogh and Hajnalka Szokolai and Thulstrup, {Peter Waaben} and Larsen, {Flemming Hofmann} and B{\'e}la Gyurcsik and Christensen, {Niels Johan} and Stachura, {Monika Kinga} and Hemmingsen, {Lars Bo Stegeager} and Attila Jancs{\'o}",

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doi = "10.1002/anie.201508555",

language = "English",

volume = "54",

pages = "15756--15761",

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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

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 -

Specificity of the metalloregulator CueR for monovalent metal ions: possible functional role of a coordinated thiol?

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