Factors controlling the selectivity for Na(+) over Mg(2+) in sodium transporters and enzymes.
Na(+) and Mg(2+) play different crucial roles in biological systems. Both cations are present in comparable amounts in the cytosol, but how monovalent Na(+) can compete with the divalent Mg(2+), which can better accept charge from negatively charged ligands, in sodium transporters/enzymes has not been investigated. Hence, it is not clear how Na(+) and Mg(2+)-binding sites have evolved to discriminate the "right" cation among non-cognate ones from the surrounding milieu and the physical basis governing the selectivity for Na(+) over Mg(2+). The results, which are consistent with available experimental data, reveal that in proteins, the selectivity for Na(+) over Mg(2+) in sodium-binding sites stem mainly from the size, charge, and charge-accepting ability differences between Na(+) and Mg(2+). A protein could achieve Na(+) selectivity by (i) reducing the number of metal-ligating ligands, (ii) maintaining an optimal balance of different ligating-strength ligands whose interactions in the metal-binding site would favor Na(+) over rival mono/divalent cations, (iii) increasing the solvent exposure of the metal-binding site, or (iv) increasing binding site rigidity forcing Mg(2+) to adopt the coordination distances/geometry of Na(+). Sodium-binding proteins use one or more of these factors to achieve Na(+) selectivity.
Faculty of Chemistry and Pharmacy, Sofia University, Sofia 1164, Bulgaria. t.dudev@chem.uni-sofia.bg.
Todor
T
Dudev
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan. carmay@gate.sinica.edu.tw and Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei 11529, Taiwan.
Karine
K
Mazmanian
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan. carmay@gate.sinica.edu.tw and Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan.
Carmay
C
Lim
D001665:Binding Sites; D002412:Cations; D002413:Cations, Divalent; D017136:Ion Transport; D008024:Ligands; D008670:Metals; D011188:Potassium / Q000737:chemistry*; D011506:Proteins / Q000378:metabolism; D012964:Sodium / Q000737:chemistry*; D012997:Solvents
D002412:Cations; D002413:Cations, Divalent; D008024:Ligands; D008670:Metals; D011506:Proteins; D012997:Solvents; D012964:Sodium; D011188:Potassium