Harper's Illustrated Biochemistry, Volume 1 - Murray R. 1993

Structure and Functions of Proteins and Enzymes
Proteins: Structure and Properties
Bonds Responsible for Protein Structure Formation

The Introduction/19.html">Primary Structure of Proteins is formed by joining L-a-Amino Acids through peptide bonds. While various data point to this Conclusion, the most compelling proof came from the Chemical synthesis of Insulin and Ribonuclease via the sequential coupling of amino acids by peptide bonds.

The structure of most proteins is stabilized by two classes of strong bonds (peptide and Disulfide Bonds) and three classes of weak bonds (hydrogen, hydrophobic, and electrostatic, i.e., salt bridges).

Rigidity of the peptide bond

In structural formulas of peptides, the bond between the carbonyl group and the a-nitrogen atom is depicted as a single bond; however, in reality, this carbon-nitrogen bond has a partial double-bond character (Fig. 5.1). Free rotation around it is impossible, and all four atoms shown in Fig. 5.1 lie in the same plane (are coplanar). Conversely, rotation around the remaining bonds of the polypeptide backbone is relatively free. This is illustrated in Fig. 5.2, where the bonds permitting free rotation are enclosed by circular arrows, while the groups of coplanar atoms are shaded. This semi-rigidity has important consequences that affect higher Levels of Protein structural Organization.

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Fig. 5.1. Resonance stabilization of the peptide bond imparts a partial double-bond character to it, which explains the rigidity of the C—N bond.

Interchain and intrachain transverse disulfide bonds

A disulfide bond forms between two Cysteine residues, "cross-linking" two segments of a polypeptide chain (or chains) to which these residues belong. This bond remains stable under conditions that normally denature proteins. Treatment of a protein with performic acid (which oxidizes S—S bonds) or ß-mercaptoethanol (which reduces S—S bonds with the regeneration of two cysteine residues) leads to the Separation of polypeptide chains linked by disulfide bonds, while their primary structure remains unaffected (see Fig. 4.10).

Stabilization of Polypeptides by interchain and intrachain Hydrogen Bonds

Hydrogen bonds form: 1) between groups within side chains that are capable of forming hydrogen bonds; 2) between nitrogen and oxygen atoms belonging to the backbone peptide groups; 3) between polar residues located on the protein surface and Water molecules. All of these play a crucial role in stabilizing secondary, tertiary, and higher-order protein structures (see the sections "a-Helix" and "Pleated ß-sheet").

Fig. 5.2. Parameters of a fully extended polypeptide chain. The four atoms located in the shaded regions are coplanar and form the peptide bond. The unshaded regions contain the a-carbon atom, the a-hydrogen atom, and the a-R-group of the corresponding amino acid. Free rotation is possible around the bonds connecting the a-carbon to the a-nitrogen and the a-carbonyl (indicated by arrows). Thus, an extended polypeptide chain is a semi-rigid structure in which two-thirds of the backbone atoms (when considering atoms grouped by the peptide bond) maintain a fixed position relative to one another and lie in the same plane. The distance between adjacent a-carbon atoms is 0.36 nm. Other interatomic distances and Bond Angles (which are nonequivalent) are also shown. (Reprinted with permission from Pauling L., Corey R. B., Branson H. R.: The structure of proteins. Two hydrogen-bonded helical configurations of the polypeptide chain. Proc. Natl. Acad. Sci. USA 1951:37:205.)

Hydrophobic interactions

Nonpolar side chains of neutral amino acids in proteins tend to associate. Stoichiometric ratios are not observed in this process, so no bonds in the conventional sense are formed. Nevertheless, these interactions play a vital role in maintaining Cell/13.html">Protein Structure.

Electrostatic bonds

These salt linkages arise between oppositely charged groups located in The amino acid side chains. For example, the ε-amino group of Lysine carries a charge of +1 at physiological pH, whereas the carboxyl group of aspartate or glutamate in a side chain carries a charge of -1. Consequently, these groups can interact electrostatically to stabilize the protein structure.

Bond strength

During Protein Denaturation (e.g., upon treatment with urea or sodium dodecyl sulfate in the presence of excess H+⁺ and OH- ions), hydrogen and Hydrophobic bonds, as well as Electrostatic Interactions, are disrupted, while peptide and disulfide bonds are preserved.