Kinins—II pp 261-271 | Cite as

Substrate Specificity of Porcine Pancreatic Kallikrein

  • Franz Fiedler
  • Gisela Leysath
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

The glandular kallikreins (EC 3.4.21.8) of the pig have revealed themselves as members of the family of pancreatic serine proteinases that includes the digestive enzymes trypsin (EC 3.4. 21.4), chymotrypsin (EC 3.4.21.1), and elastase (EC 3.4.21.11) (Tschesche et al., this volume). Outstanding in this family of proteinases is the narrow and seemingly inconsistent specificity of porcine pancreatic kallikrein. A protein as casein is hydrolyzed at least 200 times slower than it is by trypsin (Habermann 1962), though the rate of cleavage of certain specific peptide bonds may reach about 10% of the rate of tryptic attack (see below). Porcine pancreatic kallikrein contains in its sequence the same aspartic acid residue that is responsible for the specificity of trypsin for basic amino acids (Tschesche et al., this volume). Nevertheless, this kallikrein — as well as the other glandular kallikreins studied so far — exhibits the strange property of cleaving in kininogen a bond involving a neutral amino acid, methionine, with formation of kallidin. Moreover, this bond is located just adjacent to a basic lysine residue, that is readily accessible to trypsin that liberates bradykinin. In contrast, the cleavage of the second bond linking the kinin part to kininogen, an arginyl bond, conforms to the primary specificity for basic amino acids of both enzymes (Fig. 1).

Keywords

Basic Amino Acid Specificity Constant Amino Acid Ester Bovine Trypsin Hydroxy Amino 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bender, M.L. and F.J. Kezdy, 1965, Mechanism of action of proteolytic enzymes, Ann. Rev. Biochem. 34, 49.PubMedCrossRefGoogle Scholar
  2. Dittmann, B. and R. Wimmer, 1978, Comparison of kinin release and blood pressure activity of porcine pancreatic, submandibular, and urinary kallikrein. In: Current Concepts in Kínin Research, eds. G.L. Haberland and U. Hamberg (Pergamon Press, Oxford) in press.Google Scholar
  3. Fiedler, F., 1968, Heterogenitt und enzymatische Eigenschaften von Pankreaskallíkrein, Hoppe-Seylers Z. Physiol. Chem. 349, 926.Google Scholar
  4. Fiedler, F., 1976, Pig pancreatic kallikrein: structure and catalytic properties. In: Chemistry and Biology of the KallikreinKinin-System in Health and Disease, eds. J.J. Pisano and K.F. Austen ( US Government Printing Office, Washington ) p. 93.Google Scholar
  5. Fiedler, F., G. Leysath and E. Werle, 1973, Hydrolysis of aminoacid esters by pig-pancreatic kallikrein, Eur. J. Biochem. 36, 152.PubMedCrossRefGoogle Scholar
  6. Fiedler, F., W. Ehret, G. Godec, C. Hírschauer, C. Kutzbach, G. Schmidt-Kastner and H. Tschesche, 1977a, The primary structure of pig pancreatic kallikrein B. In: Kininogenases - Kallikrein, Vo. 4, eds. G.L. Haberland, J.W. Rhen and T. Suzuki ( F.K. Schattauer, Stuttgart, New York ) p. 7.Google Scholar
  7. Fiedler, F., C. Hírschauer and H. Fritz, 1966b, Inhibition of three porcine glandular kallikreins by chloromethyl ketones, HoppeSeylers Z. Physiol. Chem. 358, 447.CrossRefGoogle Scholar
  8. Fiedler, F., R. Geiger, C. Hirschauer and G. Leysath, 1978, Peptide esters and nitroanilides as substrates for the assay of human urinary kallikrein, Hoppe-Seylers Z. Physiol. Chem., in press.Google Scholar
  9. Fritz, H., F. Fiedler, T. Dietl, M. Warwas, E. Truscheit, H.J.Google Scholar
  10. Kolb, G. Mair and H. Tschesche, 1977- On the relationship between porcine pancreatic, submandíbular, and urinary kallikreins. In: Kininogenases - Kallikrein, Vol. 4, eds. G.L. Haberland, J.W. Rohen and T. Suzuki (F.K. Schattauer, Stuttgart New York) D. 15.Google Scholar
  11. Habermann, E., 1962, Trennung und Reinigung von Pankreaskallikrein, Hoppe-Seylers Z. Physiol. Chem. 328, 15.Google Scholar
  12. Habermann, E., 1966, Strukturaufklärung kíninliefernder Peptide aus Rinderserum-Kininogen, Arch. exp. Path. Pharmak. 253, 474.Google Scholar
  13. Han, Y.N., H. Kato and S. Iwanaga, 1976, Identification of Ser-LeuMet-Lys-bradykinin isolated from chemically modified highmoleculr-weight bovine kininogen, FEBS Lett. 71, 45.CrossRefGoogle Scholar
  14. Iwanaga, S., Y.N. Han, H. Kato and T. Suzuki, 1977, Actions of various kallikreins on HIM kininogen and its derivatives. In: Kininogenases - Kallikrein, Vol. 4, eds. G.L. Haberland, J.W. Rohen and T. Suzuki ( F.K. Schattauer, Stuttgart, New York ) p. 79.Google Scholar
  15. Kato, H., Y.N. Han, S. Iwanaga, N. Hashimoto, T. Sugo, S. Fuji and T. Suzuki, 1977, Mammalian plasma kininogens: their structures and functions. In: Kininogenases - Kallikrein, Vol. 4, eds. G.L. Haberland, J.W. Rohen and T. Suzuki ( F.K. Schattauer, Stuttgart, New York ) p. 63.Google Scholar
  16. Kurachi, K., J.C. Powers and P.E. Wilcox, 1973, Kinetics of the reaction of chymotrypsin An with peptide chloromethyl ketones in relation to its subsite specificity, Biochemistry 12, 771.PubMedCrossRefGoogle Scholar
  17. Lemon, M., F. Fiedler, B. Förg-Brey, C. Hischauer, G. Leysath and H. Fritz, The isolation and properties of porcine submandibular kallikrein, Biochem. J., in press.Google Scholar
  18. Schechter, I. and A. Berger, 1967, On the size of the active site in proteases: I. Papain, Biochem. Biophys. Res. Commun. 27, 157.CrossRefGoogle Scholar
  19. Schroeder, D.D. and E. Shaw, 1968, Chromatography of trypsin and its derivatives. Characterization of a new active form of bovine trypsin, J. Biol. Chem. 243, 2943.PubMedGoogle Scholar
  20. Werle, E., F. Fiedler and H. Fritz, 1973, Recent studies on kallikreins and kallikrein inhibitors. In: Pharmacology and the Future of Man, Vol. 5 ( S. Karger, Basel ) p. 284.Google Scholar

Copyright information

© Springer Science+Business Media New York 1979

Authors and Affiliations

  • Franz Fiedler
    • 1
  • Gisela Leysath
    • 1
  1. 1.Abteilung für Klinische Chemie und Klinische Biochemie der Chirurgischen KlinikUniversität MünchenMuenchen 2W. Germany

Personalised recommendations