Chemistry and Biology of Proteins - F. Haurowitz 1953

Internal Structure of Globular Proteins
Conclusion

Everything discussed in the previous sections indicates that our understanding of the Internal Structure of Proteins has advanced only slightly since Hofmeister [198] and Fischer [199]¹ first proposed their hypotheses on protein architecture in 1902. Today, there is no doubt that both globular and Fibrous proteins are composed primarily of peptide chains. Some proteins consist of a single long peptide chain, whereas others contain multiple chains, as evidenced by the presence of several terminal amino and carboxyl groups. However, we still cannot definitively state whether the peptide chains in these proteins are linked by cystine disulfide bridges, peptide or ester bonds formed by the carboxyl groups of aspartic and glutamic acids, or some other yet unknown linkages. Although cyclopeptides containing 10 or more Amino Acids have been isolated from proteins, the question of whether such polypeptide rings pre-exist in native proteins remains open.

Physicochemical and immunological studies have provided a wealth of data indicating that Globular proteins possess a rigid structure that remains intact during protein salting-out, crystallization, and dissolution. Proteins are unique in this regard. Rubber, starch, and many synthetic macromolecules alter their chain conformation upon dissolution, thereby losing the specific structure inherent to them in the solid state. In solution, the unfolded chains of these compounds can adopt countless Conformations of equivalent energy levels and, consequently, exhibit no Specificity whatsoever. Protein specificity is tied to the preservation of their internal structure, which in turn is maintained by cross-links between folded peptide chains. As noted in the previous sections, there are Three types of such linkages: 1) disulfide bridges formed by cystine; 2) salt bridges formed by the carboxyl groups of aspartic and glutamic acids and the amino groups of Lysine or the guanidino groups of Arginine; and 3) Hydrogen Bonds between peptide backbones and polar amino acid side chains.

If some or all of these bonds are cleaved, the specific internal structure of proteins is disrupted, leading to Denaturation [1].