The side chain of histidine has a pKa of 6.0, which, of all amino acid side chains, is the one closest to physiologic pH. The local environment of the protein can raise this pKa value closer to 7 such that the histidine side chains within Hb will be the major groups that accept and donate protons when Hb acts as a buffer. The alanine side chain (a methyl group) cannot accept or donate protons. The pKa for the side chains of serine or threonine are above 10.0, so at physiologic pH, these side chains are always protonated and cannot act as a binding site for excess protons generated during an acidotic event. The pKa for the side chain of aspartate is about 4.0, so at physiologic pH, that group is always deprotonated and will not accept protons generated during an acidotic event.