The Nature and Diversity of Catalytic Proteins 73 



Identification of the peptide containing the active seryl residue has 

 been made by various groups, taking advantage of the basic observa- 

 tion of Jansen, Nutting, and Balls (6), showing that with inhibition 

 by P 32 -labeled diisopropylphosphofluoridate (DFP), radioactive phos- 

 phorus became attached to an amino acid at the active site of 

 chymotrypsin. The occurrence of the same tetrapeptide sequence, 

 glycyl-aspartyl-(or glutamyl) -seryl-glycyl- in the first six enzymes 

 listed in Table 1 has given rise to the suggestion that such a sequence 

 plays an important role in the activation of the seryl hydroxyl group. 

 That such a sequence is not essential, however, is shown by the recent 

 work of Sanger and Shaw on a bacterial proteinase (5). The sequence 

 they found (Table 1 ) bears no resemblance to that found in the other 

 enzymes. Clearly more than one means is available for bringing about 

 the participation of a seryl hydroxyl in a catalytic site of a hydrolytic 

 enzyme. The occurrence of a similar sequence in the first group of 

 enzymes may actually reflect some feature other than a basic catalytic 

 requirement. 



The probability that only certain regions of enzymes participate in 

 the catalyses raises the question of whether considerable portions 

 of the amino acid chain or chains might not be essential for catalysis, 

 and, further, that much of the observed diversity of composition of 

 enzymes catalyzing a particular reaction might reside in the apparently 

 unessential portions of the protein. Our limited knowledge in this 

 area allows no generalizations as yet. With two enzymes, papain and 

 enolase, retention of activity after considerable degradation has been 

 reported. Hill and Smith (7) removed over one-half of the amino 

 acid residues from papain of mol wt about 21,000 by the action of an 

 aminopeptidase, with retention of full activity. Nylander and Malm- 

 strom (8) similarly accomplished removal of about 150 amino acid 

 residues of the yeast enolase molecule of mol wt about 66,000 from 

 either the carboxyl terminus or from the amino terminus of the 

 single peptide chain without activity loss. Some enzymes are much 

 more sensitive to degradation, however. Thus bovine pancreatic ribo- 

 nuclease of mol wt about 13.000 reversibly loses activity with removal 

 of a 20 peptide unit from the amino terminus (9). In contrast to the 

 results with papain and enolase, Drechsler, Boyer, and Kowalsky 

 (10) reported a rather striking loss in catalytic activity and change 

 in specificity of a comparatively large enzyme, rabbit muscle aldolase, 

 of mol wt 147,000, with removal of only three COOH-tcrminal tyrosyl 

 residues. 



The modification of aldolase activity accompanying removal of 



