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Heparin modulation of human plasma kallikrein on different substrates and inhibitors

  • Andrezza J. Gozzo , Viviane A. Nunes , Ilana Cruz-Silva , Adriana K. Carmona , Helena B. Nader , Adelaide Faljoni-Alario , Misako U. Sampaio and Mariana S. Araújo
Published/Copyright: August 9, 2006
Biological Chemistry
From the journal Volume 387 Issue 8

Abstract

The interplay of different proteases and glycosaminoglycans is able to modulate the activity of the enzymes and to affect their structures. Human plasma kallikrein (huPK) is a proteolytic enzyme involved in intrinsic blood clotting, the kallikrein-kinin system and fibrinolysis. We investigated the effect of heparin on the action, inhibition and secondary structure of huPK. The catalytic efficiency for the hydrolysis of substrates by huPK was determined by Michaelis-Menten kinetic plots: 5.12×104 M-1 s-1 for acetyl-Phe-Arg-p-nitroanilide, 1.40×105 M-1 s-1 for H-D-Pro-Phe-Arg-p-nitroanilide, 2.25×104 M-1 s-1 for Abz-Gly-Phe-Ser-Pro-Phe-Arg-Ser-Ser-Arg-Gln-EDDnp, 4.24×102M-1 s-1 for factor XII and 5.58×102 M-1 s-1 for plasminogen. Heparin reduced the hydrolysis of synthetic substrates (by 2.0-fold), but enhanced factor XII and plasminogen hydrolysis (7.7- and 1.4-fold, respectively). The second-order rate constants for inhibition of huPK by antithrombin and C1-inhibitor were 2.40×102 M-1 s-1 and 1.70×104 M-1 s-1, respectively. Heparin improved the inhibition of huPK by these inhibitors (3.4- and 1.4-fold). Despite the fact that huPK was able to bind to a heparin-Sepharose matrix, its secondary structure was not modified by heparin, as monitored by circular dichroism. These actions may have a function in the control or maintenance of some pathophysiological processes in which huPK participates.

Keywords: antithrombin; C1-inhibitor; factor XII; glycosaminoglycans; plasminogen; synthetic substrates
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References

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Published Online: 2006-08-09
Published in Print: 2006-08-01

©2006 by Walter de Gruyter Berlin New York

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  15. Disease processes may be reflected by correlations among tissue kallikrein proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian carcinoma
  16. Heparin modulation of human plasma kallikrein on different substrates and inhibitors
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https://doi.org/10.1515/BC.2006.139
Keywords for this article
antithrombin; C1-inhibitor; factor XII; glycosaminoglycans; plasminogen; synthetic substrates

Articles in the same Issue

  1. Caspase-containing complexes in the regulation of cell death and inflammation
  2. Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death
  3. The peptidases from fungi and viruses
  4. C. elegans as a model system to study the function of the COG complex in animal development
  5. Functional responses of bone cells to thrombin
  6. Homologous substitution of ACE C-domain regions with N-domain sequences: effect on processing, shedding, and catalytic properties
  7. Production and processing of a recombinant Fasciola hepatica cathepsin B-like enzyme (FhcatB1) reveals potential processing mechanisms in the parasite
  8. Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata
  9. Single-cell resolution imaging of membrane-anchored hepatitis C virus NS3/4A protease activity
  10. Treatment of MCF-7 cells with taxol and etoposide induces distinct alterations in the expression of apoptosis-related genes BCL2, BCL2L12, BAX, CASPASE-9 and FAS
  11. Proteolytic mechanism of a novel mitochondrial and chloroplastic PreP peptidasome
  12. Tripeptidyl-peptidase I in health and disease
  13. Molecular and functional analysis of new members of the wheat PR4 gene family
  14. C-Terminal truncations of syncytin-1 (ERVWE1 envelope) that increase its fusogenicity
  15. Disease processes may be reflected by correlations among tissue kallikrein proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian carcinoma
  16. Heparin modulation of human plasma kallikrein on different substrates and inhibitors
  17. Adaptation of the behaviour of an aspartic proteinase inhibitor by relocation of a lysine residue by one helical turn
  18. Cathepsins L and S are not required for activation of dipeptidyl peptidase I (cathepsin C) in mice
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