Acidic and Basic Side Chains

The side chains of aspartic and glutamic acids carry negatively charged carboxylate groups at pH 7 while those of lysine and arginine carry the positively charged –NH3 + and guanidinium ions, respectively.

At pH 7 the weakly basic imidazole group of histidine may be partially protonated. Both the –SH group of cysteine and the phenolic –OH of tyrosine are weakly acidic and will dissociate and thereby acquire negative charges at a sufficiently high pH.
The number of positive and negative charges on a protein at any pH can be estimated approximately from the acid dissociation constants (usually given as pKa values) for the amino acid side chains. However, pKa values of buried groups are often greatly shifted from these, especially if they associate as ion pairs. In addition, many proteins have free amino and carboxyl-terminal groups at the opposite ends of the peptide chain. These also participate in acid–base reactions with approximately the following pKa values.

terminal --, pKa = 3.6–3.7
terminal --NH3+, pKa = 7.5–7.9

The acid–base properties of an amino acid or of a protein are described by titration curves of the type. In these curves the number of equivalents of acid or base that have reacted with an amino acid or protein that was initially at neutral pH are plotted against pH. The net negative or positive electrical charge on the molecule can be read directly from the curves. Both the net electrical charges and the distribution of positively and negatively charged groups are often of crucial importance to the functioning of a protein.