Abdolvahabi, Alireza Gober, Jennifer L. Mowery, Richard A. Shi, Yunhua Shaw, Bryan F. Metal-Ion-Specific Screening of Charge Effects in Protein Amide H/D Exchange and the Hofmeister Series In this study, protein charge ladders and mass spectrometry were used to quantify how metal cations in the Hofmeister series (Na<sup>+</sup>, K<sup>+</sup>, Li<sup>+</sup>, Mg<sup>2+</sup>, and Ca<sup>2+</sup>) permute the effects of lysine acetylation on the rate of amide H/D exchange in a representative protein (myoglobin, Mb). The successive acetylation of up to 18 Lys-ε-NH<sub>3</sub><sup>+</sup> groups in Mb caused a linear decrease in its global rate of amide H/D exchange (as measured by mass spectrometry), despite also decreasing the thermostability of Mb by >10 °C. The ability of a metal cation to screen kinetic electrostatic effects during H/D exchangeand to abolish the protective effect of acetylation against H/D exchangewas found to depend on the position of the cation in the Hofmeister series. Na<sup>+</sup> and K<sup>+</sup> cations did not fully equalize the rates of H/D exchange among each “rung” of the charge ladder, whereas Mg<sup>2+</sup> and Ca<sup>2+</sup> did equalize rates without eliminating the hydrophobic core of the protein (i.e., without unfolding Mb); Li<sup>+</sup> exhibited intermediate effects. The ability of Mg<sup>2+</sup> and Ca<sup>2+</sup> to completely screen electrostatic effects associated with the H/D exchange of charge isomers of Mb suggests that Mg<sup>2+</sup> or Ca<sup>2+</sup> (but not Na<sup>+</sup> or K<sup>+</sup>) can be used to quantify the magnitude by which electrostatic charge contributes to the observed rates of amide H/D exchange in proteins. Mg;protein charge ladders;Mb;Na;amide;acetylation;cation;Hofmeister series 2014-10-21
    https://acs.figshare.com/articles/journal_contribution/Metal_Ion_Specific_Screening_of_Charge_Effects_in_Protein_Amide_H_D_Exchange_and_the_Hofmeister_Series/2242900
10.1021/ac502714v.s001