Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to characterize the heparin-binding properties of a protein secreted by mouse myeloma cells. The characterization was performed using clinical assays, such as heparin activity assays and heparin-induced thrombocytopenia (HIT) platelet activation assays. The tests were performed in the presence of heparin, low-molecular-weight heparins (LMWH), or heparinoids and either heparin-binding protein (HBP) or saline to determine whether the HBP affects the activity of heparins. The characterization of the HBP using heparin activity assays showed that the HBP shortened the prolonged clotting times of the activated partial thromboplastin time (aPTT) and thrombin clotting time induced by high concentrations of unfractionated heparin. The chromogenic assays for antithrombin (AT), thrombin inhibition, and factor Xa inhibition demonstrated that this effect is related to heparin concentrations below 0.5 IU/ml. The Heptest assay did not detect these differences. The HBP did not modify the anticoagulant effect of any LMWH or low- or high-sulfated glycosaminoglycans in the aPTT assay. Activation of donor platelets in the presence of unfractionated heparin, platelet factor 4 (PF4), and HIT-serum was not counteracted by the HBP in any of the assays. The characterization of the HBP using a PF4-enzyme-linked immunosorbent assay (ELISA) confirmed the lack of structural identity with PF4. However, the optical density data indicated that the protein structure may be similar to PF4 by binding to a PF4 antibody. These data suggest that the HBP isolated from mouse myeloma cells has a low affinity to heparin and interacts with the secondary binding site to AT and also perhaps to PF4.
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PMID:Effects of a heparin-binding protein on blood coagulation and platelet function. 1166 19

Tissue factor pathway inhibitor (TFPI) is a heparin-binding protein involved in the extrinsic blood coagulation system. In order to elucidate the minimal size of heparin chain required for the interaction with TFPI, we prepared a series of heparin-derived oligosaccharides with tailored chain length ranged from disaccharide to eicosasaccharide after the successive treatments of heparin, including partial N-desulphation, deaminative cleavage with nitrous acid and gel-filtration. Affinity chromatography study of each oligosaccharide fraction using TFPI as the ligand indicated that increasing the degree of polymerisation causes increased affinity, and that a remarkable change in the affinity occurs between the decamers and dodecamers. Measurement of factor Xa inhibitory activity of TFPI in the presence of each oligosaccharide fraction indicated that the fractions shorter than dodecamers only slightly enhanced the TFPI activity for factor Xa inhibition, while the fractions larger than octadecamers had an effect comparable to full-length heparin. These were compatible to the results from the kinetic analyses of the interaction between TFPI and heparin-derived oligosaccharide with an evanescent wave-based biosensor system, IAsys, using a TFPI C-terminal peptide as the ligand.
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PMID:Effect of heparin chain length on the interaction with tissue factor pathway inhibitor (TFPI). 1206 17

Platelet factor 4 (PF4) is a heparin-binding protein which exhibits anti-heparin activities through the inhibition of antithrombin (AT)-dependent reactions with the serine proteases thrombin and factor Xa. PF4 also neutralizes heparan sulfate (HS), a glycosaminoglycan (GAG) present on the surface of endothelial cells, thereby possibly modulating an anticoagulant response. Previous models of PF4 mechanism did not distinguish whether PF4 causes steric hindrance of AT binding to fXa or of AT binding to the surface of the GAG chain. To shed light on the mechanism of PF4, studies of HS/heparin-catalyzed fXa inactivation by AT were undertaken. The results were consistent with PF4 directly interfering with AT binding to fXa rather than AT binding to the GAG chain, since PF4 did not prevent the heparin-dependent increase in AT intrinsic fluorescence. In fact, PF4 mechanism was competitive with respect to AT and non-competitive with respect to fXa, suggesting inhibition of important regulatory/catalytic interactions of fXa with the polysaccharide. Altogether, the results suggested a model by which PF4 bound to proximal (but distinct) sites to AT, resulting in steric interference of fXa binding to both polysaccharide and AT. It is proposed that PF4 inhibited the sequence of events recapitulated in the template mechanism describing heparin-dependent inhibition of fXa.
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PMID:Platelet factor 4 neutralizes heparan sulfate-enhanced antithrombin inactivation of factor Xa by preventing interaction(s) of enzyme with polysaccharide. 1457 96