Each ionizable group of an amino acid can exist in one of two states, charged or neutral. The electric charge on the functional group is determined by the relationship between its pKa and the pH of the solution. This relationship is described by the Henderson-Hasselbalch equation.

a) histidine has three ionizable functional groups with pKas of 2.0, 6.0, and 10.0 respectively. Draw the structure of histidine in each ionization state. What is the net charge on the histidine molecule in each ionization state?

b) using structures in (a) indicate the predominant ionization structures of histidine at pH 1, 4, 8, and 12. Note that the ionization state can be approximated by treating each ionizable group independently.

c) what is the net charge of histidine at pH 1, 4, 8, and 12? do not calculate fractional charges

d) briefly describe potential roles for the imidazole side chain of histidine in primary, secondary, tertiary, and quaternary protein structure.