Molecular Basis of CLC Antiporter Inhibition by Fluoride

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Molecular Basis of CLC Antiporter Inhibition by Fluoride. / Chiariello, Maria Gabriella; Bolnykh, Viacheslav; Ippoliti, Emiliano; Meloni, Simone; Olsen, Jogvan Magnus Haugaard; Beck, Thomas; Rothlisberger, Ursula; Fahlke, Christoph; Carloni, Paolo.

In: Journal of the American Chemical Society, Vol. 142, No. 16, 04.2020, p. 7254-7258.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Chiariello, MG, Bolnykh, V, Ippoliti, E, Meloni, S, Olsen, JMH, Beck, T, Rothlisberger, U, Fahlke, C & Carloni, P 2020, 'Molecular Basis of CLC Antiporter Inhibition by Fluoride', Journal of the American Chemical Society, vol. 142, no. 16, pp. 7254-7258. https://doi.org/10.1021/jacs.9b13588

APA

Chiariello, M. G., Bolnykh, V., Ippoliti, E., Meloni, S., Olsen, J. M. H., Beck, T., Rothlisberger, U., Fahlke, C., & Carloni, P. (2020). Molecular Basis of CLC Antiporter Inhibition by Fluoride. Journal of the American Chemical Society, 142(16), 7254-7258. https://doi.org/10.1021/jacs.9b13588

CBE

Chiariello MG, Bolnykh V, Ippoliti E, Meloni S, Olsen JMH, Beck T, Rothlisberger U, Fahlke C, Carloni P. 2020. Molecular Basis of CLC Antiporter Inhibition by Fluoride. Journal of the American Chemical Society. 142(16):7254-7258. https://doi.org/10.1021/jacs.9b13588

MLA

Chiariello, Maria Gabriella et al. "Molecular Basis of CLC Antiporter Inhibition by Fluoride". Journal of the American Chemical Society. 2020, 142(16). 7254-7258. https://doi.org/10.1021/jacs.9b13588

Vancouver

Chiariello MG, Bolnykh V, Ippoliti E, Meloni S, Olsen JMH, Beck T et al. Molecular Basis of CLC Antiporter Inhibition by Fluoride. Journal of the American Chemical Society. 2020 Apr;142(16):7254-7258. https://doi.org/10.1021/jacs.9b13588

Author

Chiariello, Maria Gabriella ; Bolnykh, Viacheslav ; Ippoliti, Emiliano ; Meloni, Simone ; Olsen, Jogvan Magnus Haugaard ; Beck, Thomas ; Rothlisberger, Ursula ; Fahlke, Christoph ; Carloni, Paolo. / Molecular Basis of CLC Antiporter Inhibition by Fluoride. In: Journal of the American Chemical Society. 2020 ; Vol. 142, No. 16. pp. 7254-7258.

Bibtex

@article{712ff951c1bc49078ae5ad68e8e0ee96,
title = "Molecular Basis of CLC Antiporter Inhibition by Fluoride",
abstract = "CLC channels and transporters conduct or transport various kinds of anions, with the exception of fluoride, which acts as an effective inhibitor. Here, we performed sub-nanosecond DFT-based QM/MM simulations of the E. coli anion/proton exchanger ClC-ec1 and observed that fluoride binds incoming protons within the selectivity filter, with excess protons shared with the gating glutamate E148. Depending on E148 conformation, the competition for the proton can involve either a direct F-/E148 interaction or the modulation of water molecules bridging the two anions. The direct interaction locks E148 in a conformation that does not allow for proton transport, and thus inhibits protein function.",
keywords = "DENSITY-FUNCTIONAL THERMOCHEMISTRY, CHLORIDE CHANNEL, TRANSPORT MECHANISM, PROTON TRANSPORT, PATHWAYS, BINDING, STOICHIOMETRY, PERMEATION, REVEALS",
author = "Chiariello, {Maria Gabriella} and Viacheslav Bolnykh and Emiliano Ippoliti and Simone Meloni and Olsen, {Jogvan Magnus Haugaard} and Thomas Beck and Ursula Rothlisberger and Christoph Fahlke and Paolo Carloni",
year = "2020",
month = apr,
doi = "10.1021/jacs.9b13588",
language = "English",
volume = "142",
pages = "7254--7258",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "ACS Publications",
number = "16",

}

RIS

TY - JOUR

T1 - Molecular Basis of CLC Antiporter Inhibition by Fluoride

AU - Chiariello, Maria Gabriella

AU - Bolnykh, Viacheslav

AU - Ippoliti, Emiliano

AU - Meloni, Simone

AU - Olsen, Jogvan Magnus Haugaard

AU - Beck, Thomas

AU - Rothlisberger, Ursula

AU - Fahlke, Christoph

AU - Carloni, Paolo

PY - 2020/4

Y1 - 2020/4

N2 - CLC channels and transporters conduct or transport various kinds of anions, with the exception of fluoride, which acts as an effective inhibitor. Here, we performed sub-nanosecond DFT-based QM/MM simulations of the E. coli anion/proton exchanger ClC-ec1 and observed that fluoride binds incoming protons within the selectivity filter, with excess protons shared with the gating glutamate E148. Depending on E148 conformation, the competition for the proton can involve either a direct F-/E148 interaction or the modulation of water molecules bridging the two anions. The direct interaction locks E148 in a conformation that does not allow for proton transport, and thus inhibits protein function.

AB - CLC channels and transporters conduct or transport various kinds of anions, with the exception of fluoride, which acts as an effective inhibitor. Here, we performed sub-nanosecond DFT-based QM/MM simulations of the E. coli anion/proton exchanger ClC-ec1 and observed that fluoride binds incoming protons within the selectivity filter, with excess protons shared with the gating glutamate E148. Depending on E148 conformation, the competition for the proton can involve either a direct F-/E148 interaction or the modulation of water molecules bridging the two anions. The direct interaction locks E148 in a conformation that does not allow for proton transport, and thus inhibits protein function.

KW - DENSITY-FUNCTIONAL THERMOCHEMISTRY

KW - CHLORIDE CHANNEL

KW - TRANSPORT MECHANISM

KW - PROTON TRANSPORT

KW - PATHWAYS

KW - BINDING

KW - STOICHIOMETRY

KW - PERMEATION

KW - REVEALS

U2 - 10.1021/jacs.9b13588

DO - 10.1021/jacs.9b13588

M3 - Journal article

C2 - 32233472

VL - 142

SP - 7254

EP - 7258

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 16

ER -