Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clearance of thrombin seems to occur at more than one site and by different mechanisms. This contributes to maintaining thrombin at the right concentrations to act optimally on its various substrates, and thus, to produce the proper amount of proteolytic conversions so that coagulation is precisely controlled. The vascular endothelium plays a major role in thrombin regulation and clearance. It contains heparin-like binding sites and thrombomodulin which serve as cofactors for the thrombin-antithrombin III reaction and the activation of protein C, respectively. In addition, thrombomodulin also serves as a receptor for endothelial cell mediated thrombin endocytosis. Thrombin clearance, which occurs following reaction with antithrombin III or thrombomodulin, probably takes place at different stages in hemostasis.
Mol Cell Biochem 1986 Aug
PMID:Clearance of thrombin in vivo: significance of alternative pathways. 302 20

Human apolipoprotein E is a component of several classes of circulating plasma lipoproteins. In addition to binding lipids, this apolipoprotein, which is composed of two structural domains, mediates some lipoprotein-receptor interactions by binding to the low density lipoprotein receptor. The receptor-binding function, as well as some lipid-binding capability, is contained in the amino-terminal structural domain of apolipoprotein E. Thrombin-catalyzed hydrolysis of apolipoprotein E yields a fragment (residues 1 to 191) that has the same properties as, and seems to be a good model for, the amino-terminal domain. Crystals of this amino-terminal fragment suitable for high-resolution X-ray diffraction experiments have now been grown. The crystals belong to the orthorhombic space group P2(1)2(1)2(1) and have unit cell dimensions of a = 86.0 A, b = 40.9 A, and c = 53.3 A (1 A = 0.1 nm). This is the first human serum apolipoprotein to be crystallized.
J Mol Biol 1988 Jul 05
PMID:Crystallization and preliminary X-ray diffraction studies on the amino-terminal (receptor-binding) domain of human apolipoprotein E3 from serum very low density lipoproteins. 317 12

Fluid phase heparin inhibits formation of the classical and alternative pathway C3 convertase of complement in assays performed either with purified complement proteins or in whole serum. Experiments using oligosaccharides of homogeneous mol. wt obtained by mild nitrous hydrolysis of heparin, demonstrated that the inhibitory activity of heparin increased exponentially with mol. wt for fragments containing between 4 and 14 saccharidic units and that fragments of mol. wt above 4700 (greater than 14 saccharidic units) had a similar anti-complementary activity to that of native heparin. Fragments of homogeneous mol. wt (octasaccharides) separated by ion exchange chromatography on the basis of negative charges, exhibited increasing inhibitory activity with increasing sulfate content. Over-sulfation of fragments of defined mol. wt resulted in a constant enhancement of the relative capacity of each fragment species to inhibit formation of the classical and alternative pathway C3 convertases. A synthetic pentasaccharide representing the minimal critical sequence responsible for the binding of heparin to anti-thrombin III exhibited a similar inhibitory capacity on formation of the C3 convertases as another synthetic pentasaccharide that was devoid of anti-Xa activity. These studies contribute to define a minimal structure of the heparin molecule with C3b- and C4b-binding capacity and definitively establish the independency of the anti-coagulant and anti-complementary sites on the heparin molecule.
Mol Immunol 1988 Sep
PMID:Structure-function relationships in the inhibitory effect of heparin on complement activation: independency of the anti-coagulant and anti-complementary sites on the heparin molecule. 321 Nov 61

The use of derivatives of alpha-thrombin obtained by limited proteolysis, that have only a single peptide bond cleaved, allowed the unequivocal correlation between the change in covalent structure and alteration of the enzymatic properties. beta T-Thrombin contains a single cleavage in the surface loop corresponding to residues 65-83 of alpha-chymotrypsin [Birktoft, J. J., & Blow, D. M. (1972) J. Mol. Biol. 68, 187-240]. Compared with alpha-thrombin, this modification had a minor effect on the following: (1) The Michaelis constant (Km) for two tripeptidyl p-nitroanilide substrates increased 2-3 fold, whereas the catalytic constant (k cat) remained unaltered. (2) A 2-3 fold increase in the binding constant (KI) of a tripeptidyl chloromethane inhibitor was observed, but the inactivation rate constant (k i) was the same, which indicated that the nucleophilicity of the active-site histidyl residue had not changed. (3) The second-order rate constant for the inhibition by antithrombin III decreased 2-fold. Heparin accelerated the inactivation, and the degree of acceleration was similar to that obtained with alpha-thrombin. Pronounced effects of the cleavage of this loop were found. (1) The cleavage of fibrinogen was approximately 80-fold slower than that with alpha-thrombin. This was mainly due to a 40-fold decrease in k cat. In contrast, only a 1.9-fold increase in the Michaelis constant was observed. (2) The affinity for thrombomodulin had decreased 39-fold compared to alpha-thrombin. epsilon-Thrombin contains a single cleaved peptide bond in the loop corresponding to residues 146-150 in alpha-chymotrypsin.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Enzymatic properties of proteolytic derivatives of human alpha-thrombin. 337 50

We investigated the binding of C4 and C3 to red cell surfaces by non-complement enzymes. Cell bound C components were quantitated by a radioimmunoassay, the chain structure of bound components was analyzed by Western blotting and the hemolytic activity of bound components was determined. Trypsin, chymotrypsin, plasmin, elastase, thrombin, kallikrein and enzymes from Bacillus subtilis, Staphylococcus aureus and Streptomyces griseus all were found capable of binding C4b and C3b to sheep red cells. C4b bound by any of these enzymes was hemolytically active; both classical and alternate pathway activity of C3 could be demonstrated for most enzymes except plasmin and thrombin. In addition, trypsin and the bacterial enzymes were also able to generate the classical pathway C3-convertase from C4b + C2. The hemolytic efficiency of enzyme bound C4b and C3b was about the same as for these molecules bound by complement enzymes. In contrast, the process of binding by the non-complement enzymes was several hundred-fold less efficient than by cell bound complement enzymes. The results demonstrate that several enzymes can replace the C1 and C42 enzymes in the classical pathway and are able to initiate the alternative pathway by activating C3 and binding C3b to the cell surface.
Mol Immunol 1988 May
PMID:Binding and activation of C4 and C3 on the red cell surface by non-complement enzymes. 341 32

The obligatory role of the endothelium in relaxations of isolated coronary arteries to acetylcholine is explained by the release by endothelial cells of a labile vasodilator substance(s), endothelium-derived relaxing factor(s). Other neurohumoral mediators can evoke endothelium-dependent relaxations of coronary arteries. Of particular importance from the clinical point of view are thrombin, serotonin and adenine nucleotides. The latter are chiefly responsible for the endothelium-dependent relaxations evoked by aggregating platelets. The absence or the dysfunction of the endothelium may favour the occurrence of vasospasm.
J Mol Cell Cardiol 1986 Jul
PMID:Could the absence or malfunction of vascular endothelium precipitate the occurrence of vasospasm? 352 7

This study evaluated ultrastructures of cell membrane-cytoskeletal interactions in resting and activated human blood platelets. Some blood platelets were fixed with paraformaldehyde to inhibit activation and the others were activated with thrombin treatment. The replicas of inside-out cell membranes, cell membrane surfaces, and Triton shells were made by the quick-freezing and deep-etching replica method. A geometrical pattern consisting of main hexagons and partial pentagons was revealed to be formed with microfilaments which were attached laterally to cytoplasmic sides of cell membranes in resting platelets. After the activation, cytoskeletal meshworks in the cytoplasm were densely associated with cell membranes, and parallel microfilamentous bundles in filopodia were connected with small polygonal meshworks lying under the cell membrane. The cell membrane-cytoskeletal interactions are essential to keeping a discoid shape at the resting stage, and to changing the shape quickly after the activation.
J Ultrastruct Mol Struct Res
PMID:Attachment of cytoskeletons to cell membranes in human blood platelets as revealed by the quick-freezing and deep-etching replica method. 361 52

The contributions of various regions of human alpha-thrombin to the formation of the tight complex with hirudin have been assessed by using derivatives of thrombin. alpha-Thrombin in which the active-site serine was modified with diisopropyl fluorophosphate was able to bind hirudin, but its affinity for hirudin was decreased by 10(3)-fold compared to unmodified alpha-thrombin. Modification of the active-site histidine with D-Phe-Pro-Arg-CH2Cl resulted in a form of thrombin with a 10(6)-fold reduced affinity for hirudin. gamma-Thrombin is produced by proteolytic cleavage of alpha-thrombin in two surface loops corresponding to residues 65-83 and 146-150 in alpha-chymotrypsin [Berliner, L. J. (1984) Mol. Cell. Biochem. 61, 159-172; Birktoft, J. J., & Blow, D. M. (1972) J. Mol. Biol. 68, 187-240]. The gamma-thrombin-hirudin complex had a dissociation constant that was 10(6)-fold higher than that of alpha-thrombin. Treatment of alpha-thrombin with pancreatic elastase resulted in a form of thrombin only cleaved in the loop corresponding to residues 146-150 in alpha-chymotrypsin, and this form of thrombin had only a slightly reduced affinity for hirudin. By using limited proteolysis with trypsin, it was possible to isolate beta-thrombin which contained a single cleavage in the loop corresponding to residues 65-83 in alpha-chymotrypsin. This form of thrombin had a 100-fold decrease in affinity for hirudin. Kinetic analysis of the binding of hirudin to beta-thrombin indicated that the 100-fold decrease in affinity was predominantly due to a decrease in the rate of association of the two molecules.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Identification of regions of alpha-thrombin involved in its interaction with hirudin. 366 13

Interactions between fibrin and arterial endothelial cells of rat iliac arteries in vivo were studies electron microscopically using a newly devised method. The microvilli became attached to the fibrin threads in an initial period of fibrinolysis. These threads had a fine granular appearance in the lysed areas. Fibrinolytically active endothelial cells had an active vesicular transport for ferritin particles injected concomitantly with the fibrinogen-thrombin mixture, thereby implying the enhancement of endothelial permeability in the lysed areas. However, fibrinolytically inactive endothelial cells coexisted in the same arteries. The denuded intima showed no lytic changes in the fibrin threads. These results indicate that the microvilli of the endothelial cells may plan an important role in the releasing plasminogen tissue activator from the endothelial cells and that there is a heterogeneity with regard to reactivity of each endothelial cell to fibrin.
Exp Mol Pathol 1986 Jun
PMID:Pathophysiological effects of fibrin on arterial endothelial cells in vivo: an electron microscopic study. 372 Sep 24

This paper is intended as a background to the topic of transglutaminases, while focusing on current ideas regarding the biological roles of these enzymes. Specifically, the following topics are discussed: geometry of forming gamma-glutamyl-epsilon-lysine cross-linked structures; energetic considerations; the gamma-glutamyl-epsilon-lysine cross-link; amine incorporation assays; artefactual incorporation of amines in cells and tissue homogenates; synthetic substrate systems; regulation of transglutaminase activities; strategies for probing transglutaminase-mediated events in biological systems; the blood clotting paradigm; transglutaminase and cell aging: the Ca2+-enriched human erythrocyte; transglutaminase and cell activation: the thrombin-stimulated human platelet and the fertilized sea urchin egg.
Mol Cell Biochem 1984
PMID:Transglutaminases. 614 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>