|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 November 2000, Vol. 96, No. 9, pp. 3049-3055
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Characterization of the protein Z-dependent protease
inhibitor
Xin Han,
Ryan Fiehler, and
George J. Broze Jr
From the Division of Hematology, Barnes-Jewish Hospital
at Washington University Medical Center, St Louis, MO.
Protein Z-dependent protease inhibitor (ZPI) is a 72-kd
member of the serpin superfamily of proteinase inhibitors that produces rapid inhibition of factor Xa in the presence of protein Z (PZ), procoagulant phospholipids, and Ca++ (t1/2 less
than 10 seconds). The rate of factor Xa inhibition by ZPI is reduced
more than 1000-fold in the absence of PZ. The factor Xa-ZPI complex is
not stable to sodium dodecyl sulfate-polyacrylamide gel
electrophoresis, but is detectable by alkaline-polyacrylamide gel
electrophoresis. The combination of PZ and ZPI dramatically delays the
initiation and reduces the ultimate rate of thrombin generation in
mixtures containing prothrombin, factor V, phospholipids, and
Ca++. In similar mixtures containing factor Va, however, PZ
and ZPI do not inhibit thrombin generation. Thus, the major effect of PZ and ZPI is to dampen the coagulation response prior to the formation
of the prothrombinase complex. Besides factor Xa, ZPI also inhibits
factor XIa in the absence of PZ, phospholipids, and Ca++.
Heparin (0.2 U/mL) enhances the rate (t1/2 = 25 seconds
vs 50 seconds) and the extent (99% vs 93% at 30 minutes) of
factor XIa inhibition by ZPI. During its inhibitory interaction with
factor Xa and factor XIa, ZPI is proteolytically cleaved with
the release of a 4.2-kd peptide. The N-terminal amino acid
sequence of this peptide (SMPPVIKVDRPF) establishes Y387 as the
P1 residue at the reactive center of ZPI. ZPI activity is
consumed during the in vitro coagulation of plasma through a
proteolytic process that involves the actions of factor Xa with PZ
and factor XIa.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Z. Wei, Y. Yan, R. W. Carrell, and A. Zhou
Crystal structure of protein Z-dependent inhibitor complex shows how protein Z functions as a cofactor in the membrane inhibition of factor X
Blood,
October 22, 2009;
114(17):
3662 - 3667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. W. Gettins and S. T. Olson
Exosite Determinants of Serpin Specificity
J. Biol. Chem.,
July 31, 2009;
284(31):
20441 - 20445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Rezaie, J.-S. Bae, C. Manithody, S. H. Qureshi, and L. Yang
Protein Z-dependent Protease Inhibitor Binds to the C-terminal Domain of Protein Z
J. Biol. Chem.,
July 18, 2008;
283(29):
19922 - 19926.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Zhang, Y. Tu, L. Lu, N. Lasky, and G. J. Broze Jr
Protein Z-dependent protease inhibitor deficiency produces a more severe murine phenotype than protein Z deficiency
Blood,
May 15, 2008;
111(10):
4973 - 4978.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Burggraf, B. Dorhofer, and B. Olgemoller
Hybridization Probe Genotyping of the R67X Nonsense Polymorphism in the Protein Z-Dependent Protease Inhibitor Reveals a New R67Q Mutation
Clin. Chem.,
July 1, 2007;
53(7):
1385 - 1387.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Abo and V. A. DeBari
Laboratory Evaluation of the Antiphospholipid Syndrome
Ann. Clin. Lab. Sci.,
January 1, 2007;
37(1):
3 - 14.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Corral, R. Gonzalez-Conejero, J. M. Soria, J. R. Gonzalez-Porras, E. Perez-Ceballos, R. Lecumberri, V. Roldan, J. C. Souto, A. Minano, D. Hernandez-Espinosa, et al.
A nonsense polymorphism in the protein Z-dependent protease inhibitor increases the risk for venous thrombosis
Blood,
July 1, 2006;
108(1):
177 - 183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Heeb, K. M. Cabral, and L. Ruan
Down-regulation of Factor IXa in the Factor Xase Complex by Protein Z-dependent Protease Inhibitor
J. Biol. Chem.,
October 7, 2005;
280(40):
33819 - 33825.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Rezaie, C. Manithody, and L. Yang
Identification of Factor Xa Residues Critical for Interaction with Protein Z-dependent Protease Inhibitor: BOTH ACTIVE SITE AND EXOSITE INTERACTIONS ARE REQUIRED FOR INHIBITION
J. Biol. Chem.,
September 23, 2005;
280(38):
32722 - 32728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y Shoenfeld and M Blank
Autoantibodies associated with reproductive failure
Lupus,
September 1, 2004;
13(9):
643 - 648.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. M. McQuillan, J. W. Eikelboom, G. J. Hankey, R. Baker, J. Thom, J. Staton, Q. Yi, and V. Cole
Protein Z in Ischemic Stroke and its Etiologic Subtypes
Stroke,
October 1, 2003;
34(10):
2415 - 2419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-C. Gris, C. Amadio, E. Mercier, G. Lavigne-Lissalde, H. Dechaud, M. Hoffet, I. Quere, J. Amiral, M. Dauzat, and P. Mares
Anti-protein Z antibodies in women with pathologic pregnancies
Blood,
June 15, 2003;
101(12):
4850 - 4852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Crowther and J. G. Kelton
Congenital Thrombophilic States Associated with Venous Thrombosis: A Qualitative Overview and Proposed Classification System
Ann Intern Med,
January 21, 2003;
138(2):
128 - 134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-C. Gris, I. Quere, H. Dechaud, E. Mercier, C. Pincon, M. Hoffet, M. Vasse, and P. Mares
High frequency of protein Z deficiency in patients with unexplained early fetal loss
Blood,
April 1, 2002;
99(7):
2606 - 2608.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
