Inhibition of porcine glandular kallikreins by structurally homologous proteinase inhibitors of the Kunitz (Trasylol) type. Significance of the basic nature of amino acid residues in subside positions for kallikrein inhibition.
The newly synthesized chromogenic substrate D ValLeuArgNHNp was employed to study the inhibition strength of Trasylol-like inhibitors from bovine lung (TKI), sea anemone (SAI), snake venoms (NNV and HHV), snails (HPI) and cow colostrum (CTI) against porcine pancreatic, submandibular and urinary kallikreins. The dissociation constants of the corresponding kallikrein-inhibitor complexes were found close to Ki = 1.5 x 10(-9)M (TKI, SAI, NNV) or to Ki = 10--210 x 10(-9)M (HHV, HPI). CTI does not inhibit the three porcine glandular kallikreins. Comparison of the inhibitory active areas of the inhibitors with their affinities to the three kallikreins shows that kallikrein inhibition is observed only if basic amino acid residues are present in distinct positions of the inhibitory active sites.
D000595:Amino Acid Sequence; D000818:Animals; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D010179:Pancreas / Q000201:enzymology; D011480:Protease Inhibitors / Q000494:pharmacology*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013363:Submandibular Gland / Q000201:enzymology; D013552:Swine; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D014360:Trypsin Inhibitor, Kunitz Soybean; D007610:Kallikreins