This title appears in the Scientific Report :
2020
Please use the identifier:
http://dx.doi.org/10.1021/jacs.9b13588 in citations.
Please use the identifier: http://hdl.handle.net/2128/25668 in citations.
Molecular Basis of CLC Antiporter Inhibition by Fluoride
Molecular Basis of CLC Antiporter Inhibition by Fluoride
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 prot...
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Personal Name(s): | Chiariello, Maria Gabriella (Corresponding author) |
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Bolnykh, Viacheslav / Ippoliti, Emiliano / Meloni, Simone / Olsen, Jógvan Magnus Haugaard / Beck, Thomas / Rothlisberger, Ursula / Fahlke, Christoph (Corresponding author) / Carloni, Paolo (Corresponding author) | |
Contributing Institute: |
Molekular- und Zellphysiologie; IBI-1 Computational Biomedicine; INM-9 Computational Biomedicine; IAS-5 |
Published in: | Journal of the American Chemical Society, 142 (2020) 16, S. 7254 - 7258 |
Imprint: |
Washington, DC
American Chemical Society
2020
|
DOI: |
10.1021/jacs.9b13588 |
PubMed ID: |
32233472 |
Document Type: |
Journal Article |
Research Program: |
FOR 2518: Funktionale Dynamik von Ionenkanälen und Transportern - DynIon - Theory, modelling and simulation |
Link: |
Published on 2020-04-01. Available in OpenAccess from 2021-04-01. Published on 2020-04-01. Available in OpenAccess from 2021-04-01. |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/25668 in citations.
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. |