TY  - JOUR
AU  - Chiariello, Maria Gabriella
AU  - Bolnykh, Viacheslav
AU  - Ippoliti, Emiliano
AU  - Meloni, Simone
AU  - Olsen, Jógvan Magnus Haugaard
AU  - Beck, Thomas
AU  - Rothlisberger, Ursula
AU  - Fahlke, Christoph
AU  - Carloni, Paolo
TI  - Molecular Basis of CLC Antiporter Inhibition by Fluoride
JO  - Journal of the American Chemical Society
VL  - 142
IS  - 16
SN  - 1520-5126
CY  - Washington, DC
PB  - American Chemical Society
M1  - FZJ-2020-03078
SP  - 7254 - 7258
PY  - 2020
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.
LB  - PUB:(DE-HGF)16
C6  - pmid:32233472
UR  - <Go to ISI:>//WOS:000529156100003
DO  - DOI:10.1021/jacs.9b13588
UR  - https://juser.fz-juelich.de/record/884077
ER  -