Disease relevance of MGC127984

• These data indicate that antithrombin III may play a role in the progression of HIV-1 disease [1].
• Antithrombin III-independent effect of depolymerized holothurian glycosaminoglycan (DHG) on acute thromboembolism in mice [2].
• Hereditary deficiency of antithrombin-III (AT-III), the major heparin cofactor in human plasma, is a well-established cause of recurrent venous thrombosis [3].
• Our data indicate that anti-viral inactive ATIII can be activated having promising anti-viral properties as complementary candidate for the treatment of HIV infection [4].
• Antithrombin III levels in the plasma appeared to drop during anaphylaxis but were not significantly depressed (p greater than or equal to 0.5) [5].

High impact information on MGC127984

• It was inhibited by diisopropyl phosphorofluoridate and antithrombin III, suggesting that it is a serine enzyme [6].
• The concentrations of 13 plasma proteins and complexes of thrombin and Factor Xa with antithrombin III were measured in synovial fluids recovered at the time of knee replacement surgery [7].
• The inhibitory potency of heparin was not dependent upon its affinity for antithrombin III, but was molecular weight dependent: homogeneous preparations of lower molecular weight were less inhibitory [8].
• Bovine antithrombin III (AT III) interaction with the luminal surface of bovine aortic segments with a continuous layer of endothelium was examined [9].
• Addition of antibody to antithrombin III prevented formation of Factor Xa-antithrombin III and thrombin-antithrombin III complexes in the supernatant and increased apparent thrombin activity 30-50-fold [10].

Biological context of MGC127984

• The most significant difference between ATIII and alpha 1-antitrypsin lies in the 45 residue N-terminal extension in ATIII which contribute to the definition of the heparin binding site [11].
• The complete amino acid sequence of bovine antithrombin (ATIII) [12].
• The cell adhesion promoting activity of NO2-alpha-thrombin was blocked upon the formation of thrombin-antithrombin III (ATIII) complexes and by antiprothrombin antibodies, but was unaffected by hirudin [13].
• The inhibition of thrombin by antithrombin III (AT III) and heparin has been studied in pure systems to determine the kinetics of inhibition during human prothrombin activation [14].
• Platelet factor 3 vesicles, isolated from platelet aggregation supernatants, also formed prothrombinase complex in the presence of factor Va, and this was inhibited by antithrombin III at the same rate as the platelet-bound complex [15].

Anatomical context of MGC127984

• Identification in vitro of an endothelial cell surface cofactor for antithrombin III. Parallel studies with isolated perfused rat hearts and microcarrier cultures of bovine endothelium [16].
• With each preparation, accelerated inhibition of thrombin by antithrombin III occurred during passage over endothelium [16].
• Two in vitro systems were used to identify an antithrombin III cofactor activity on vascular endothelium [16].
• Newly synthesized heparan sulfates purified from the cell layer of bovine aortic endothelial cells (BAECs) and main pulmonary artery endothelial cells (BPAECs) cultured under either normoxic (21% oxygen) or hypoxic (3% oxygen) conditions were characterized by size, charge, and capacity to bind to antithrombin III [17].
• Purification of a modified form of bovine antithrombin III as an HIV-1 CD8+ T-cell antiviral factor [1].

Associations of MGC127984 with chemical compounds

• Docking of the pentasaccharide unit which represents the minimum fragment of heparin able to bind to ATIII indicates a possible role for arginine 14 in the interaction of heparin and the protein [11].
• Bovine antithrombin (ATIII) is a glycoprotein of Mr 56,600 [12].
• Platelet factor 4, protamine sulfate and diisopropylphosphoryl thrombin, all antagonists of the antithrombin III cofactor activity of heparin, significantly reduced the capacity of the preparation to inhibit thrombin [16].
• The deduced amino acid sequence has extensive (30%) homology with alpha 1-antitrypsin and antithrombin III, indicating that the beta-PAI is a member of the serine proteinase inhibitor (serpin) superfamily [18].
• Comparable results are obtained with ATIII modified at a single tryptophan residue [19].

Regulatory relationships of MGC127984

• These data suggest that prothrombin fragment 2 may be an important factor in controlling the localization of clot formation by regulating the interaction between thrombin and antithrombin III [20].

Other interactions of MGC127984

• The apparent efficiency of prothrombin activation, however, is dampened by the presence of functional antithrombin III on the vessel wall [10].
• As predicted from the x-ray structure, des-PPW is remarkably sensitive to the bovine pancreatic trypsin inhibitor, with a K(i) over 3 x 10(3) times tighter relative to thrombin, but des-PPW is also markedly less susceptible to inactivation by antithrombin III, with a k(on) that is over 100-fold lower [21].
• Inhibition of thrombin bound to cultured bovine aortic endothelial cells (BAEC) by ATIII and the effect of the inhibitor on the activation of PC has been studied using purified components of bovine origin [22].
• Of these molecules, antithrombin III and basic fibroblast growth factor have been shown to bind to specific cell surface heparan sulfate proteoglycans [23].
• While Heparin-Membrane Adsorber were found to isolate and concentrate the Antithrombin III efficiently, the removal of the major bovine serum proteins (albumin, transferrin, immunoglobulins) required a multistage process [24].

Analytical, diagnostic and therapeutic context of MGC127984

• In addition, nonreducing SDS-PAGE demonstrated that HNE-treated F.IX formed no complexes with antithrombin III (ATIII) in the presence of heparin [25].
• Also, after treatment with factor XIa, none of the Bm variants reacted with antithrombin III (in contrast to normal factor IXa) [26].
• Crystallization and preliminary crystallographic data for bovine antithrombin III [27].
• Studies of heparin binding to antithrombin III by crossed immunoelectrophoresis [28].
• The heavy-chain regions, containing the active site serine and histidine residues, were normal in the abnormal proteins on the basis of titration by antithrombin III [29].

References