The joining of the 20 amino acids commonly found in proteins is accomplished through peptide bonds. The linear sequence of these amino acids contains the necessary information to create a protein molecule with a distinct three-dimensional shape, which ultimately determines its function. To understand the complexity of protein structure, it is helpful to consider it in terms of four organizational levels: primary, secondary, tertiary, and quaternary. The analysis of these levels has revealed that certain structural elements are repeated in various proteins, suggesting general principles for achieving the native and functional form of proteins. These repeated structural elements can range from simple combinations of α-helices and β-sheets forming small motifs to the intricate folding of polypeptide domains in multifunctional proteins.

The primary structure of a protein refers to the sequence of amino acids in the protein. Understanding the primary structure is crucial because genetic diseases can result in proteins with abnormal amino acid sequences, leading to improper folding and the loss or impairment of normal function. By knowing the primary structures of both normal and mutated proteins, it becomes possible to diagnose or study the disease.

In proteins, amino acids are covalently joined together by peptide bonds, which are amide linkages connecting the α-carboxyl group of one amino acid to the α-amino group of another. For instance, valine and alanine can form the dipeptide valylalanine through the formation of a peptide bond. Peptide bonds are resistant to conditions that denature proteins, such as heating and high concentrations of urea. Nonenzymatic breaking of these bonds requires prolonged exposure to a strong acid or base at elevated temperatures.

When naming a peptide, the convention is to write the free amino end (N-terminal) of the peptide chain to the left and the free carboxyl end (C-terminal) to the right. Consequently, all amino acid sequences are read from the N-terminal to the C-terminal end. For example, in Figure 2.2A, the order of the amino acids in the dipeptide is valine, alanine. Linking ≥50 amino acids through peptide bonds results in an unbranched chain known as a polypeptide or protein. Each individual amino acid component is referred to as a residue because it is the remaining portion of the amino acid after the loss of water atoms during the formation of the peptide bond. When naming a peptide, all amino acid residues have their suffixes (-ine, -an, -ic, or -ate) changed to -yl, except for the C-terminal amino acid. For instance, a tripeptide composed of an N-terminal valine, a glycine, and a C-terminal leucine is called valylglycylleucine.

The peptide bond possesses a partial double-bond character, making it shorter and rigid compared to a single bond. This rigidity prevents free rotation around the bond between the carbonyl carbon and the nitrogen of the peptide bond. However, the bonds between the α-carbons and the α-amino or α-carboxyl groups can be freely rotated, albeit within limits imposed by the size and nature of the R groups. This flexibility allows the polypeptide chain to assume various conformations. The peptide bond is typically in the trans configuration, rather than the cis configuration, primarily due to steric interference of the R groups (side chains) when in the cis position.
The 20 amino acids commonly found in proteins are joined together by peptide bonds. The linear sequence of the linked amino acids contains the information necessary to generate a protein molecule with a unique three-dimensional shape that determines function. The complexity of protein structure is best analyzed by considering the molecule in terms of four organizational levels: primary, secondary, tertiary, and quaternary (Fig. 2.1). An examination of these hierarchies of increasing complexity has revealed that certain structural elements are repeated in a wide variety of proteins, suggesting that there are general rules regarding the ways in which proteins achieve their native, functional form. These repeated structural elements range from simple combinations of α-helices and β-sheets forming small motifs to the complex folding of polypeptide domains of multifunctional proteins (see p. 19).
II. PRIMARY STRUCTURE
The sequence of amino acids in a protein is called the primary structure of the protein. Understanding the primary structure of proteins is important because many genetic diseases result in proteins with abnormal amino acid sequences, which cause improper folding and loss or impairment of normal function. If the primary structures of the normal and the mutated proteins are known, this information may be used to diagnose or study the disease.
A. Peptide bond
In proteins, amino acids are joined covalently by peptide bonds, which are amide linkages between the α-carboxyl group of one amino acid and the αamino group of another. For example, valine and alanine can form the dipeptide valylalanine through the formation of a peptide bond (Fig. 2.2). Peptide bonds are resistant to conditions that denature proteins, such as heating and high concentrations of urea (see p. 20). Prolonged exposure to a strong acid or base at elevated temperatures is required to break these bonds nonenzymically (see p. 14).
1.
Naming the peptide: By convention, the free amino end (N-terminal) of the peptide chain is written to the left and the free carboxyl end (C-terminal) to the right. Therefore, all amino acid sequences are read from the N-to the C-terminal end. For example, in Figure 2.2A, the order of the amino acids in the dipeptide is valine, alanine. Linkage of ≥50 amino acids through peptide bonds results in an unbranched chain called a polypeptide, or protein. Each component amino acid is called a residue because it is the portion of the amino acid remaining after the atoms of water are lost in the formation of the peptide bond. When a peptide is named, all amino acid residues have their suffixes (-ine, -an, -ic, or -ate) changed to -yl, with the exception of the C-terminal amino acid. For example, a tripeptide composed of an N-terminal valine, a glycine, and a C-terminal leucine is called valylglycylleucine.
2.
Peptide bond characteristics: The peptide bond has a partial double-bond character, that is, it is shorter than a single bond and is rigid and planar (Fig. 2.2B). This prevents free rotation around the bond between the carbonyl carbon and the nitrogen of the peptide bond. However, the bonds between the α-carbons and the α-amino or α-carboxyl groups can be freely rotated (although they are limited by the size and character of the R groups). This allows the polypeptide chain to assume a variety of possible conformations. The peptide bond is almost always in the trans configuration (instead of the cis; see Fig. 2.2B), in large part because of steric interference of the R groups (side chains) when in the cis position.
3.