Proteins consist of α-L-amino acids linked by peptide bonds to form polypeptide chains (Fig.1). At neutral pH, the carboxyl group of a free amino acid is negatively charged and the amino group is positively charged. In a protein, however, these charges are largely, but not completely absent from the interior amino acids owing to the formation of the peptide bonds between the amino groups and carboxyl groups. Of course, the N-terminal amino group of a protein is positively charged and the C-terminal carboxyl group is negatively charged.

Fig1. An α-L-amino acid with negative charge on the carboxyl and positive charge on the amino group and three amino acids linked by peptide bonds.

Twenty different types of α-L-amino acids are commonly found in proteins (Fig. 2). Except for proline, which technically is an imino acid, these differ from one another only in the structure of the side group attached to the alpha carbon. A few other types of amino acids are occasionally found in proteins, with most resulting from modification of one of the twenty after the protein has been synthesized. Frequently these modified amino acids are directly involved with chemical reactions catalyzed by the protein. Each of the basic twenty must possess unique and invaluable properties since most proteins contain all twenty different amino acids (Table 1).

Fig2. The side chains of amino acids and their single letter abbreviations. The complete structure of proline is shown. The most hydrophobic amino acids are at the top and the most hydrophilic are at the bottom.

Table1. Properties of Amino Acids

Even though we must understand the individual properties of each of the amino acids, it is convenient to classify the twenty into a smaller number of groups and to understand common properties of the groups. One of the most important such groups is the hydrophobics. The side groups of the aliphatic amino acids are hydrophobic and prefer to exist in a nonaqueous, nonpolar environment like that found in the contact region between two subunits, in the portion of a protein bound to a membrane, or in the interior of a globular protein. A contiguous area of such amino acids on a portion of the surface can make a protein bind to a similar hydrophobic patch on the surface of another protein, as in the oligomerization of protein subunits, or it can make the protein prefer to bind to or even enter a membrane. Hydrophobic amino acids on the interior of a protein prefer the company of one another to the exclusion of water. This is one of the major forces that maintains the structure of a folded protein.

The basic amino acid side groups of amino acids like lysine and arginine possess a positive charge at neutral pH. If located on the surface of the protein, such positive charges can assist the binding of a negatively charged ligand, for example DNA. The acidic amino acid side groups of glutamic acid and aspartic acid possess a negative charge at neutral pH. Neutral amino acid side groups possess no net charge, and polar amino acid side groups possess separated charges like those found on glutamine. Separated charges lead to dipole interactions with other amino acids or with ligands binding to the protein.

Cysteine is a notable unique amino acid since in an oxidizing extracellular environment, but not in the intracellular environment, two cysteine residues in a protein can spontaneously oxidize to form a rather stable disulfide bond (Fig.3). In the isolated protein, this bond can be reduced by the presence of an excess of a reducing reagent to regenerate cysteines.

Fig3. Two reduced cysteine residues and their oxidized state, which forms a disulfide bond.