Journal Article

FZJ-2020-03078

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Molecular Basis of CLC Antiporter Inhibition by Fluoride

Chiariello, M. G. (Corresponding author)FZJ* ; Bolnykh, V.FZJ* ; Ippoliti, E.FZJ* ; Meloni, S. ; Olsen, J. M. H.Extern* ; Beck, T. ; Rothlisberger, U.Extern* ; Fahlke, C. (Corresponding author)FZJ* ; Carloni, P. (Corresponding author)FZJ*

2020
American Chemical Society Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/25668  doi:10.1021/jacs.9b13588

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.

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Contributing Institute(s):

1. Computational Biomedicine (IAS-5)
2. Computational Biomedicine (INM-9)
3. Molekular- und Zellphysiologie (IBI-1)

Research Program(s):

1. 574 - Theory, modelling and simulation (POF3-574) (POF3-574)
2. DFG project 291198853 - FOR 2518: Funktionale Dynamik von Ionenkanälen und Transportern - DynIon - (291198853)

Appears in the scientific report 2020

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; Index Chemicus ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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