Glutamate water gates in the ion binding pocket of Na+ bound Na+,K+ -ATPase

Minwoo Han, Wojciech Kopec, Ilia A. Solov'yov, Himanshu Khandelia
Scientific Reports
7
39829
2017
abstract
The dynamically changing protonation states of the six acidic amino acid residues in the ion bindingpocket of the Na+, K+ -ATPase (NKA) during the ion transport cycle are proposed to drive ion
binding, release and possibly determine Na+ or K+ selectivity. We use molecular dynamics (MD) and
density functional theory (DFT) simulations to determine the protonation scheme of the Na+ bound
conformation of NKA. MD simulations of all possible protonation schemes show that the bound Na+
ions are most stably bound when three or four protons reside in the binding sites, and that Glu954 in
site III is always protonated. Glutamic acid residues in the three binding sites act as water gates, and
their deprotonation triggers water entry to the binding sites. From DFT calculations of Na+ binding
energies, we conclude that three protons in the binding site are needed to effectively bind Na+ from
water and four are needed to release them in the next step. Protonation of Asp926 in site III will induce
Na+ release, and Glu327, Glu954 and Glu779 are all likely to be protonated in the Na+ bound occluded
conformation. Our data provides key insights into the role of protons in the Na+ binding and release
mechanism of NKA.