ENZYMIC HYDROLYSIS 



AND SYNTHESIS OF 



PEPTIDE BONDS 



JOSEPH S. FRUTON, associate professor of physiological 



CHEMISTRY, YALE UNIVERSITY; LILLY AWARD IN BIOLOGICAL CHEMISTRY 



Specificity of Proteolytic Enzymes 



THE ACTION of proteolytic enzymes on peptide linkages 

 involves a high degree of specificity. No proteolytic 

 enzyme acts on peptide bonds indiscriminately, and each enzyme 

 hydrolyzes only such peptide bonds as are present in the substrate in 

 a certain structural setting. Thus, the nature of the requisite struc- 

 tural attributes of the substrate is an expression of the specificity of the 

 enzyme which hydrolyzes the substrate. In recent years, much 

 attention has been devoted to the determination of those structural 

 elements in the substrate molecule which are essential for the action of 

 various proteolytic enzymes. These studies have permitted the formu- 

 lation of several hypotheses concerning the specific action of the pro- 

 teolytic enzymes. 



Modern theories concerning the specificity of proteolytic 

 enzymes are based on the assumption, made by von Euler and Joseph- 

 sohn (17) in their "dual-affinity" theory, that ereptic peptidase— it 

 was not recognized at that time that "erepsin" represents a mixture of 

 many peptidases — combines with two atomic groupings of the sub- 

 strate molecule. Subsequent work of Balls and Kohler (2) presented 



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