The inhibition of pepsin-catalysed reactions by structural and stereochemical product analogues.
1. The inhibition of pepsin-catalysed hydrolysis of N-acetyl-l-phenylalanyl-l-phenylalanylglycine by products and product analogues was studied. 2. Inhibitors of the l-configuration give rise to linear non-competitive inhibition, whereas those of the d-configuration show linear competitive behaviour. 3. Non-competitive inhibition by the product N-acetyl-l-phenylalanine indicates an ordered release of products, which supports a common mechanism (involving an ;amino-enzyme') for pepsin-catalysed transpeptidation and hydrolysis reactions. 4. The differences in the types of inhibition caused by product analogues of the l- and d-series emphasize the stereospecificity of the binding of these inhibitors to free enzyme and to the putative amino-enzyme intermediate. 5. The results suggest that it is the anion of the acyl product that is released first in the hydrolytic reaction (see Kitson & Knowles, 1971).
D000577:Amides / Q000494:pharmacology; D004952:Esters / Q000494:pharmacology; D005998:Glycine; D007700:Kinetics; D010434:Pepsin A / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000494:pharmacology; D010649:Phenylalanine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000577:Amides; D004952:Esters; D010455:Peptides; D010649:Phenylalanine; D010434:Pepsin A; D005998:Glycine