The intact and cleaved human antithrombin III complex as a model for serpin–proteinase interactions

@article{Schreuder1994TheIA,
  title={The intact and cleaved human antithrombin III complex as a model for serpin–proteinase interactions},
  author={Herman Schreuder and B. de Boer and Rein Dijkema and John W. M. Mulders and Henri J. M. Theunissen and Peter D. J. Grootenhuis and Wim G. J. Hol},
  journal={Nature Structural Biology},
  year={1994},
  volume={1},
  pages={48-54}
}
Antithrombin is a member of the serine proteinase inhibitor (serpin) family which contain a flexible reactive site loop that interacts with, and is cleaved by the target proteinase. In cleaved and latent serpins, the reactive site loop is inserted into a large central β–sheet in the same molecule, whereas in ovalbumin, a nonfunctional serpin, the reactive site loop is completely exposed and in an α–helical conformation. However, in neither conformation can the reactive site loop bind to target… Expand
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TLDR
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Antithrombin III: structural and functional aspects.
TLDR
The X-ray structure of antithrombin III has been determined and the overall topology is similar to that of alpha 1-antitrypsin, another member of the serpin (serine protease inhibitor) superfamily. Expand
Crystal structure of ovalbumin as a model for the reactive centre of serpins
TLDR
The structure of native ovalbumin is determined to 1.95 Å resolution and it is found that the intact peptide loop forming the analogue to the reactive centre of the inhibitory serpins takes the unexpected form of a protruding, isolated helix. Expand
Mobile reactive centre of serpins and the control of thrombosis
TLDR
It is shown here that the reactive centre of the serpins can adopt varying conformations and that mobility of the reactive centres is necessary for the function of antithrombin and its binding and activation by heparin and the identification of a new locked conformation explains the latent inactive state of PAI-1. Expand
Conformation of the reactive site loop of alpha 1-proteinase inhibitor probed by limited proteolysis.
TLDR
It is concluded that the A-sheet of virgin alpha 1-proteinase inhibitor resembles that of ovalbumin, except that it contains a bulge where two or three RSL residues are inserted. Expand
Crystal structure of cleaved human alpha 1-antichymotrypsin at 2.7 A resolution and its comparison with other serpins.
The crystal structure of proteolytically modified human alpha 1-antichymotrypsin (ACT), a member of the serpin superfamily, has been solved by Paterson search techniques and refined to an R-factor ofExpand
Crystal structure of cleaved bovine antithrombin III at 3.2 A resolution.
TLDR
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. Expand
Structural basis of latency in plasminogen activator inhibitor-1
TLDR
The structure of intact latent PAI-1 determined by single-crystal X-ray diffraction reveals that residues on the N-terminal side of the primary recognition site are inserted as a central strand of the largest βsheet, in positions similar to the corresponding residues in the cleaved form of the serpin α1proteinase inhibitor (α1-PI). Expand
Serpins: Mobile conformations in a family of proteinase inhibitors
TLDR
The structures of three alternative conformations are now known, and it can be deduced that the active form involves the partial insertion of the loop into the A sheet of the molecule. Expand
Constructing a molecular model of the interaction between Antithrombin-III and a potent synthetic heparin Analogue.
Abstract: Information about the antithrombin 111-heparin interaction is deduced from the following: (i) structure-activity studies of various synthetic analogues of the antithrombin I11 bindingExpand
Self-association of antithrombin III relates to multimer formation of thrombin-antithrombin III complexes.
  • K. Preissner
  • Chemistry, Medicine
  • Thrombosis and haemostasis
  • 1993
TLDR
Self-association products of the ternary vitronectin-thrombin-AT III complex, which is the ultimate reaction product following thrombin inhibition in the circulation, could be recognized and quantitated due to exposure of the 4C9 epitope on AT III, indicating that AT III exists in multimeric forms within binary and ternARY complexes. Expand
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