Thrombomodulin is an endothelial cell thrombin receptor that converts thrombin from a procoagulant to an anticoagulant enzyme [<cite idref="PUB00000529"/>, <cite idref="PUB00002467"/>]. Thrombomodulin forms a 1:1 stoichiometric complex with thrombin that is responsible for the conversion ofprotein C to the activated protein CA. Protein CA scissions the activated cofactors of the coagulation mechanism, factors VA and VIIIA, and thereby reduces the amount of thrombin generated.<p> The thrombin-bound structures of peptide fragments from the fifth EGF-like domain of thrombomodulin have been determined by NMR and transferred NOE spectroscopy [<cite idref="PUB00005040"/>]. The peptides assume an EGF-like structure, with an anti-parallel beta-sheet, which shows structural resilience in accommodating different numbers of residues within its disulphide loop. The key contacts with thrombin are hydrophobic interactions between the side chains of residues Ile 414 and Ile 424 of thrombomodulin and a hydrophobic pocket on the thrombin surface. The unique beta-sheet structures of the bound peptides are specified by the presence of disulphide bridges; corresponding linear thrombomodulin fragments fold into sheet structures with different backbone topologies.</p>