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. 1983 Jul;80(13):3928–3932. doi: 10.1073/pnas.80.13.3928

Kinetic analysis of the interaction of human tissue kallikrein with single-chain human high and low molecular weight kininogens.

M Maier, K F Austen, J Spragg
PMCID: PMC394172  PMID: 6575386

Abstract

Human low molecular weight kininogen (LMWK) and high molecular weight kininogen (HMWK) have been purified to apparent homogeneity as intact, single-chain molecules. When they interacted with homologous urinary kallikrein, 0.9 mol of kinin per mol of substrate was released from LMWK and 0.7 mol of kinin per mol of substrate was released from HMWK. These functionally and structurally intact substrates have been used to obtain the kinetic constants for kinin release by purified human tissue kallikreins. With human urinary kallikrein, apparent second-order rate constants (kcat/Km) of 1.46 X 105, 8.6 X 104, and 5.08 X 104 M-1.S-1 were obtained with LMWK, HMWK, and alpha-N-p-tosyl-L-arginine methyl ester (TAMe), respectively; with human pancreatic kallikrein, values of 8.7 X 103 and 7.3 X 104 M-1.S-1 were obtained with HMWK and TAMe. These values, which are comparable to those obtained for other enzyme-protein substrate interactions, indicate that LMWK is only slightly preferred to interactions, indicate that LMWK is only slightly preferred to HMWK as the natural substrate for urinary kallikrein and that HMWK as the natural substrate for urinary kallikrein and that HMWK is a somewhat better substrate for urinary kallikrein than for pancreatic kallikrein. Although the data obtained have been shown by NaDodSO4/polyacrylamide gel electrophoresis to reflect cleavage of the substrate at two points, the linear Line-weaver-Burk plots suggest that one cleavage is rate limiting. Because the plasma concentrations of both LMWK and HMWK are approximately 1/10th the Km values obtained, substrate concentration may also play a role in determining the rate at which tissue kallikreins release kinins from kininogen substrates either in the circulation or extravascularly.

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Selected References

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  1. Ascenzi P., Menegatti E., Guarneri M., Bortolotti F., Antonini E. Catalytic properties of serine proteases. 2. Comparison between human urinary kallikrein and human urokinase, bovine beta-trypsin, bovine thrombin, and bovine alpha-chymotrypsin. Biochemistry. 1982 May 11;21(10):2483–2490. doi: 10.1021/bi00539a030. [DOI] [PubMed] [Google Scholar]
  2. Bajaj S. P. Cooperative Ca2+ binding to human factor IX. Effects of Ca2+ on the kinetic parameters of the activation of factor IX by factor XIa. J Biol Chem. 1982 Apr 25;257(8):4127–4132. [PubMed] [Google Scholar]
  3. Colman R. W., Bagdasarian A., Talamo R. C., Scott C. F., Seavey M., Guimaraes J. A., Pierce J. V., Kaplan A. P. Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways. J Clin Invest. 1975 Dec;56(6):1650–1662. doi: 10.1172/JCI108247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dittmann B., Steger A., Wimmer R., Fritz H. A convenient large-scale preparation of high molecular weight kininogen from human plasma. Hoppe Seylers Z Physiol Chem. 1981 Jul;362(7):919–927. doi: 10.1515/bchm2.1981.362.2.919. [DOI] [PubMed] [Google Scholar]
  5. Fink E., Seifert J., Geiger R., Güttel C. Studies on the physiological function of glandular kallikrein by radioimmunoassay. Adv Biosci. 1978 Jul 22;17:111–119. [PubMed] [Google Scholar]
  6. Geiger R., Clausnitzer B., Fink E., Fritz H. Isolation of an enzymatically active glandular kallikrein from human plasma by immunoaffinity chromatography. Hoppe Seylers Z Physiol Chem. 1980 Dec;361(12):1795–1803. doi: 10.1515/bchm2.1980.361.2.1795. [DOI] [PubMed] [Google Scholar]
  7. Habal F. M., Movat H. Z., Burrowes C. E. Isolation of two functionally different kininogens from human plasma--separation from proteinase inhibitors and interaction with plasma kallikrein. Biochem Pharmacol. 1974 Aug 15;23(16):2291–2303. doi: 10.1016/0006-2952(74)90558-9. [DOI] [PubMed] [Google Scholar]
  8. Hamberg U., Elg P., Nissinen E., Stelwagen P. Purification and heterogeneity of human kininogen. Use of DEAE-chromatography, molecular sieving and antibody specific immunosorbents. Int J Pept Protein Res. 1975;7(3):261–280. [PubMed] [Google Scholar]
  9. Kato H., Han Y. N., Iwanaga S., Suzuki T., Komiya M. Bovine plasma HMW and LMW kininogens. Structural differences between heavy and light chains derived from the kinin-free proteins. J Biochem. 1976 Dec;80(6):1299–1311. doi: 10.1093/oxfordjournals.jbchem.a131402. [DOI] [PubMed] [Google Scholar]
  10. Kerbiriou D. M., Bouma B. N., Griffin J. H. Immunochemical studies of human high molecular weight kininogen and of its complexes with plasma prekallikrein or kallikrein. J Biol Chem. 1980 May 10;255(9):3952–3958. [PubMed] [Google Scholar]
  11. Kerbiriou D. M., Griffin J. H. Human high molecular weight kininogen. Studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma. J Biol Chem. 1979 Dec 10;254(23):12020–12027. [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. Leytus S. P., Peltz G. A., Liu H. Y., Cannon J. F., Peltz S. W., Livingston D. C., Brocklehurst J. R., Mangel W. F. A quantitative assay for the activation of plasminogen by transformed cells in situ and by urokinase. Biochemistry. 1981 Jul 21;20(15):4307–4314. doi: 10.1021/bi00518a011. [DOI] [PubMed] [Google Scholar]
  14. Lottspeich F., Geiger R., Henschen A., Kutzbach C. N-Terminal amino acid sequence of human urinary kallikrein homology with other serine proteases. Hoppe Seylers Z Physiol Chem. 1979 Dec;360(12):1947–1950. [PubMed] [Google Scholar]
  15. Matheson R. T., Miller D. R., Lacombe M. J., Han Y. N., Iwanaga S., Kato H., wuepper K. D. Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen. J Clin Invest. 1976 Dec;58(6):1395–1406. doi: 10.1172/JCI108595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mori K., Nagasawa S. Studies on human high molecular weight (HMW) kininogen. II. Structural change of HMW kininogen by the action of human plasma kallikrein. J Biochem. 1981 May;89(5):1465–1473. doi: 10.1093/oxfordjournals.jbchem.a133339. [DOI] [PubMed] [Google Scholar]
  17. Mori K., Sakamoto W., Nagasawa S. Studies on human high molecular weight (HMW) kininogen. III. Cleavage of HMW kininogen by the action of human salivary kallikrein. J Biochem. 1981 Aug;90(2):503–509. doi: 10.1093/oxfordjournals.jbchem.a133498. [DOI] [PubMed] [Google Scholar]
  18. Mori K., Sakamoto W., Nagasawa S. Studies on human high molecular weight (HMW) kininogen. III. Cleavage of HMW kininogen by the action of human salivary kallikrein. J Biochem. 1981 Aug;90(2):503–509. doi: 10.1093/oxfordjournals.jbchem.a133498. [DOI] [PubMed] [Google Scholar]
  19. Nustad K., Gautvik K., Orstavik T. Radioimmunoassay of rat submandibular gland kallikrein and the detection of immunoreactive antigen in blood. Adv Exp Med Biol. 1979;120A:225–234. doi: 10.1007/978-1-4757-0926-1_23. [DOI] [PubMed] [Google Scholar]
  20. Proud D., Bailey G. S., Nustad K., Gautvik K. M. The immunological similarity of rat glandular kallikreins. Biochem J. 1977 Dec 1;167(3):835–838. doi: 10.1042/bj1670835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Proud D., Perkins M., Pierce J. V., Yates K. N., Highet P. F., Herring P. L., Mangkornkanok/Mark M., Bahu R., Carone F., Pisano J. J. Characterization and localization of human renal kininogen. J Biol Chem. 1981 Oct 25;256(20):10634–10639. [PubMed] [Google Scholar]
  22. Saito H., Ratnoff O. D., Waldmann R., Abraham J. P. Fitzgerald Trait: Deficiency of a Hitherto Unrecognized Agent, Fitzgerald Factor, Participating in Surface-Mediated Reactions of Clotting, Fibrinolysis, Generation of Kinins, and the Property of Diluted Plasma Enhancing Vascular Permeability (PF/Dil). J Clin Invest. 1975 May;55(5):1082–1089. doi: 10.1172/JCI108009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sakamoto W., Nishikaze O. Purification and immunochemical properties of human low molecular weight kininogen. J Biochem. 1979 Nov;86(5):1549–1557. doi: 10.1093/oxfordjournals.jbchem.a132672. [DOI] [PubMed] [Google Scholar]
  24. Schiffman S., Mannhalter C., Tyner K. D. Human high molecular weight kininogen. Effects of cleavage by kallikrein on protein structure and procoagulant activity. J Biol Chem. 1980 Jul 10;255(13):6433–6438. [PubMed] [Google Scholar]
  25. Scicli A. G., Waldmann R., Guimaraes J. A., Scicli G., Carretero O. A., Kato H., Han Y. N., Iwanaga S. Relation between structure and correcting activity of bovine high molecular weight kininogen upon the clotting time of Fitzgerald-trait plasma. J Exp Med. 1979 Apr 1;149(4):847–855. doi: 10.1084/jem.149.4.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Spragg J., Austen K. F. the preparation of human kininogen. II. Further characterization of purified human kininogen. J Immunol. 1971 Dec;107(6):1512–1519. [PubMed] [Google Scholar]
  27. Spragg J., Haber E., Austen K. F. The preparation of human kininogen and the elicitation of antibody for use in a radial immuno-diffusion assay. J Immunol. 1970 Jun;104(6):1348–1354. [PubMed] [Google Scholar]
  28. Thompson R. E., Mandle R., Jr, Kaplan A. P. Characterization of human high molecular weight kininogen. Procoagulant activity associated with the light chain of kinin-free high molecular weight kininogen. J Exp Med. 1978 Feb 1;147(2):488–499. doi: 10.1084/jem.147.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Vogel C. W., Müller-Eberhard H. J. The cobra venom factor-dependent C3 convertase of human complement. A kinetic and thermodynamic analysis of a protease acting on its natural high molecular weight substrate. J Biol Chem. 1982 Jul 25;257(14):8292–8299. [PubMed] [Google Scholar]
  30. WEBSTER M. E., EMMART E. W., TURNER W. A., MORIYA H., PIERCE J. V. Immunological properties of the kallikreins. Biochem Pharmacol. 1963 May;12:511–519. doi: 10.1016/0006-2952(63)90230-2. [DOI] [PubMed] [Google Scholar]
  31. Wiggins R. C., Bouma B. N., Cochrane C. G., Griffin J. H. Role of high-molecular-weight kininogen in surface-binding and activation of coagulation Factor XI and prekallikrein. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4636–4640. doi: 10.1073/pnas.74.10.4636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wohl R. C., Summaria L., Robbins K. C. Kinetics of activation of human plasminogen by different activator species at pH 7.4 and 37 degrees C. J Biol Chem. 1980 Mar 10;255(5):2005–2013. [PubMed] [Google Scholar]
  33. Wuepper K. D., Miller D. R., Lacombe M. J. Flaujeac trait. Deficiency of human plasma kininogen. J Clin Invest. 1975 Dec;56(6):1663–1672. doi: 10.1172/JCI108248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yoi O. O., Austen K. F., Spragg J. Kinin-generating and esterolytic activity of purified human urinary kallikrein (urokallikrein). Biochem Pharmacol. 1977 Oct 15;26(20):1893–1900. doi: 10.1016/0006-2952(77)90163-0. [DOI] [PubMed] [Google Scholar]
  35. Yoi O. O., Seldin D. C., Spragg J., Pinkus G. S., Austen K. F. Sequential cleavage of proinsulin by human pancreatic kallikrein and a human pancreatic kininase. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3612–3616. doi: 10.1073/pnas.76.8.3612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. ole-Moi Yoi O., Spragg J., Halbert S. P., Austen K. F. Immunologic reactivity of purified human urinary kallikrein (urokallikrein) with antiserum directed against human pancreas. J Immunol. 1977 Feb;118(2):667–672. [PubMed] [Google Scholar]
  37. ole-MoiYoi O. K., Spragg J., Austen K. F. Inhibition of human urinary kallikrein (urokallikrein) by anti-enzyme FAB. J Immunol. 1978 Jul;121(1):66–71. [PubMed] [Google Scholar]
  38. ole-MoiYoi O. K., Spragg J., Austen K. F. Structural studies of human urinary kallikrein (urokallikrein). Proc Natl Acad Sci U S A. 1979 Jul;76(7):3121–3125. doi: 10.1073/pnas.76.7.3121. [DOI] [PMC free article] [PubMed] [Google Scholar]

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