HYDROLYSIS OF PEPTIDE BONDS 



To our knowledge, the proteolytic enzymes represent the first 

 class of enzymes for which liie property of homospecificity has been 

 demonstrated. It is not unlikely, however, that similar relationships 

 may exist in other classes of enzymes. Some years ago, the question 

 was raised whether the hydrolysis of the various /3-glucosides by emulsin 

 is to be attributed to a single iS-glucosidase or to several glucosidases 

 of slightly different specificity, and also whether the emulsins of various 

 plants contain identical or diff'erent /3-glucosidases. In particular, 

 Weidenhagen (33) advocated the theory that the emulsins from various 

 sources contain the same /3-D-glucosidase, and that this enzyme splits 

 not only all /3-D-glucosides containing various aglucones, but also all 

 oligosaccharides in which the sugar components are linked through 

 /3-D-glucosidic linkage. More recently, Pigman (28), in his classi- 

 fication of carbohydrases, suggested that the individual enzymes of 

 Weidenhagen's system be considered as classes of enzymes acting on the 

 same substrates but with different specificities. The finding of homo- 

 specific proteolytic enzymes now raises the question whether similar 

 groups of carbohydrases of identical specificity type exist. It may be 

 added that Bisseger and Zeller (13) have applied the concept of homo- 

 specificity to choline esterases obtained from various tissues. 



Mechanism of Enzymic Proteolysis 



It is inviting to speculate about the structural factors in the 

 enzyme which give rise to the phenomenon of homospecificity. It was 

 mentioned earlier that each proteolytic enzyme requires, for its action, 

 certain atomic groupings in the backbone of its substrates. This 

 backbone specificity may perhaps best be explained by the hypothesis 

 that each enzyme molecule contains an essential center, composed of 

 several distinct atomic groupings in a definite arrangement, and that 

 the first step of enzymic action consists in a combination of several 

 atomic groupings of the essential center of the enzyme with the indis- 

 pensable backbone groups o' the substrate. As in the Michaelis 

 concept of the enzyme-substrate compound, it is assumed that this 

 combination would result in the activation, and subsequent hydrolysis, 

 of an adjacent peptide bond of the substrate. To explain the homo- 

 specificity phenomenon, it seems necessary to conclude that the 

 enzymic action and its specificity originate from a rather restricted area 



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