Rommie Amaro, Emad Tajkhorshid, and Zaida Luthey-Schulten.
Developing an energy landscape for the novel function of a
(β/α)8 barrel: Ammonia conduction through HisF.
Proceedings of the National Academy of Sciences, USA,
100:7599-7604, 2003.
AMAR2003-ZL
Water transport channels in membrane proteins of the aquaporin superfamily are impermeable to ions, including H and OH. We examine the molecular basis for the blockage of proton translocation through the single-file water chain in the pore of a bacterial aquaporin, GlpF. We compute the reversible thermodynamic work for the two complementary steps of the Grotthuss “hop-and-turn” relay mechanism: consecutive transfers of H along the hydrogen-bonded chain (hop) and conformational reorganization of the chain (turn). In the absence of H, the strong preference for bipolar orientation of water around the two Asn-Pro-Ala (NPA) motifs lining the pore over both unidirec-
tional polarization states of the chain precludes the reorganization of the hydrogen-bonded network. Inversely, translocation of an excess proton in either direction is opposed by a free-energy barrier centered at the NPA region. Both hop and turn steps of proton translocation are opposed by the electrostatic field of the channel.
