Importance of secondary enzyme-substrate interactions in human cathepsin G and chymotrypsin II catalysis

Abstract The active center of human leukocyte cathepsin G, human pancreatic chymotrypsin II, and bovine α-chymotrypsin has been investigated with a series of substrates of general formula succinyl-( l -alanine) n -phenylalanine- p -nitroanilide ( n = 0 to 3). The three proteinases have an extended substrate binding site which includes at least six subsites. Secondary interactions are very important for their catalytic power since the longest substrate is hydrolyzed 600 to 1100 times faster than the shortest one. The regulatory subsite is S 4 for bovine α-chymotrypsin and human cathepsin G whereas it is S 5 for human chymotrypsin II. Cathepsin G is a poor catalyst compared to the two other enzymes.