All peptides and proteins, regardless of their origin, are constructed from amino acids that are covalently linked together, usually in a linear sequence. Twenty-one amino acids are naturally incorporated into polypeptides in mammals. Twenty of these are directly encoded by the universal genetic code. The twenty-first of the amino acid precursors for protein synthesis, selenocysteine, is incorporated into a small number of proteins by a unique cotranslational mechanism requiring special secondary structure in the messenger RNA (mRNA) (i.e., a selenocysteine insertion sequence, SECIS) that causes the UGA stop codon to encode selenocysteine (see Chapter 39). Another unusual amino acid called pyrrolysine is considered the twenty-second proteinogenic amino acid, but it is found only in some methane-producing enzymes in methanogenic archaea. The structures of the 20 common amino acids and selenocysteine are shown in Figure 5-1. In aqueous solutions, amino acids are easily ionized. The most abundant ionic species present when amino acids are dissolved in an aqueous medium at neutral pH are shown in Figure 5-1, and the pKas for all dissociable groups are shown in Table 5-1. The acid dissociation constant Ka is used to define characteristics of titratable groups in organic acids and amines. The negative log of the dissociation constant Ka is called the pKa of the titratable group. In a practical sense, this means that when the pH is equal to the pKa, the associated (AH, protonated) and dissociated (A–, unprotonated) species will be present in equal molar concentrations. TABLE 5-1 Properties of the Amino Acids That Serve as Common Building Blocks of Proteins The presence of a titratable group can be easily observed on a titration curve as a marked decrease in the change in pH per unit of base added; this will appear as a flattening of the curve when pH is plotted on the vertical axis and units of base are plotted on the horizontal axis. In essence, the titratable group acts as a buffer to resist changes in pH by donating protons to neutralize the base that is added. A curve obtained by the titration of histidine, which contains three titratable functional groups, is shown in Figure 5-3. On a titration curve, the pKa can be observed as the point of inflection near the center of the “plateau.” The inflection point is where the curvature changes from concave up to concave down. For histidine in Figure 5-3, three pKas can be detected: the carboxyl group has a pKa = 1.82 the imidazole group has a pKa = 6.0, and the α-amino group has a pKa = 9.17. Jack Kyte and Russell Doolittle (1982) proposed a hydropathy index that is now widely used to predict aspects of protein structure; this scale assigns negative numbers to the most hydrophilic side chains and positive numbers to the most hydrophobic side chains (see Table 5-1). Other scales have been developed, some of which assign quite different values to some of the amino acids. Efforts to develop better methods of predicting protein structure continue. An example of the use of a hydropathy index to predict the transmembrane segments of a protein sequence is shown in Figure 5-4. Transmembrane segments of transmembrane proteins can be predicted from the average hydrophobicity scores for small regions of the polypeptide chain (e.g., segments of 9 to 19 amino acids). Transmembrane regions of proteins, which must pass through the lipid bilayers of cell membranes, tend to have high hydropathy scores (greater than 1.6 units).
Structure, Nomenclature, and Properties of Proteins and Amino Acids
The Proteinogenic Amino Acids
The Acid and Base Characteristics of Amino Acids
AMINO ACID
MOLECULAR MASS (g/mol)
pKa α-COOH
pKa α-NH3+
pKa R GROUP
HYDROPATHY INDEX (KYTE-DOOLITTLE SCALE)
Hydrophilic amino acids (charged and very polar)
Arginine
155
2.17
9.04
12.48
−4.5
Lysine
146
2.18
8.95
10.53
−3.9
Asparagine
132
2.04
9.82
−3.5
Aspartate
133
2.09
9.82
3.86
−3.5
Glutamine
146
2.17
9.13
−3.5
Glutamate
147
2.19
9.67
4.25
−3.5
Histidine
174
1.82
9.17
6.0
−3.2
Amino acids with intermediate hydrophobicity (Tyr and moderately/weakly polar amino acids)
Tyrosine
181
2.20
10.07
9.11
−1.3
Tryptophan
204
2.38
9.39
−0.9
Serine
105
2.21
9.15
−0.8
Threonine
119
2.63
10.43
−0.7
Glycine
75
2.34
9.60
−0.4
Proline
115
1.99
10.6 (NH2+)
1.6
Alanine
89
2.34
9.69
1.8
Methionine
149
2.28
9.31
1.9
Cysteine
121
1.71
10.78
8.33
2.5
Hydrophobic amino acids (uncharged and nonpolar)
Phenylalanine
165
1.83
9.13
2.8
Leucine
131
2.36
9.68
3.8
Valine
117
2.32
9.62
4.2
Isoleucine
131
2.36
9.68
4.5
Hydrophobicity or Hydrophilicity of Amino Acid Residues