Enzymology of porcine tissue kallikrein.
In the pig, submandibular, native pancreatic, and urinary kallikreins are the same protein, consisting of a single polypeptide chain (alpha-kallikrein). Porcine tissue kallikrein shows very extensive sequence homology with several enzymes from submandibular glands of rats and mice, tonin, nerve growth factor gamma subunit, and submandibular proteinase A, nearly as high as with human urinary or rat submandibular kallikrein. Porcine pancreatic kallikrein isolated from partial autolyzates of pancreas carries an intrachain split (beta-kallikrein). Both chains exist in a high and low molecular weight form each because of differences in their carbohydrate content and form four types of pancreatic beta-kallikrein (B, A, III, and C). One cause of the narrow specificity of tissue kallikrein is their pronounced secondary specificity for a bulky, hydrophobic amino acid residue in P2. The hydrolysis of 10 peptide esters Ac-X-ArgOMe with different amino acids in P2 by porcine pancreatic kallikrein also showed distinct individual influences, the most favorably residues being phenylalanine and leucine as they occur in bovine kininogen. In contrast, specificity constants for hydrolysis by the digestive enzyme trypsin are similar for all these compounds. A peptide with the amino acid sequence around the methionyl bond cleaved in kininogen is also hydrolyzed by pancreatic kallikrein at this bond, but with a specificity constant three orders of magnitude lower. The lack of cleavage at lysine leading to the release of kallidin instead of bradykinin is due to the inability of porcine pancreatic kallikrein to accommodate an Arg-Pro leaving group.
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D006868:Hydrolysis; D007609:Kallidin / Q000378:metabolism; D007610:Kallikreins / Q000032:analysis* / Q000494:pharmacology / Q000652:urine; D051379:Mice; D010179:Pancreas / Q000201:enzymology*; D051381:Rats; D013363:Submandibular Gland / Q000201:enzymology*; D013379:Substrate Specificity; D013552:Swine
D007609:Kallidin; D007610:Kallikreins