Chemistry and Biology of Proteins - F. Haurowitz 1953

Proteins with Enzymatic Properties
Conclusion

From the extensive data presented in this chapter, it follows that A large number of Proteins function either as Enzymes or as apoenzymes. Although there is no doubt that the enzymatic activity of proteins stems from specific chemical Features of the protein molecule's Structure, we still know nothing definitive about these particular features. Further research must determine whether enzymatic activity depends on the presence of significant amounts of Certain Amino Acids, on their specific arrangement, or, ultimately, on some other factors.

When comparing The properties of enzyme proteins with those of other proteins, it is readily apparent that many enzyme proteins possess a relatively low molecular weight and high stability against heating in slightly acidic solutions. The low Molecular Weight of many enzymes, their heat resistance, and their pronounced ability to crystallize indicate that Proteins with Enzymatic Properties consist of units with a highly rigid internal structure that have little tendency to form large aggregates. This internal rigidity is possibly due to the presence of numerous cross-links between the peptide chains. Amino acid analyses of Pepsin and Chymotrypsin have shown that these proteins contain unusually large amounts of hydroxyamino acids: Serine and Threonine (see Table 1). Since every hydroxyl group is capable of forming a Hydrogen bond, the presence of these amino acids increases the potential for cross-linking. Furthermore, the presence of a large number of hydroxyl groups in the protein molecule brings about substantial intermolecular attraction, which may thus facilitate both the binding of the enzyme to the substrate and the alteration of the attached substrate molecule.

At present, these concepts cannot yet be extended to all enzymes, since the Amino Acid Composition is known for only a few of them. Consequently, we cannot yet provide a satisfactory explanation for the underlying causes of protein enzymatic activity and must limit ourselves to the hypothesis stated above, namely, that a high number of polar groups in the protein molecule accounts for its structural rigidity and the generation of significant attractive forces on the enzyme molecule's surface.