THE INTACT AND CLEAVED HUMAN ANTITHROMBIN-III COMPLEX AS A MODEL FOR SERPIN-PROTEINASE INTERACTIONS

Antithrombin is a member of the serine proteinase inhibitor (serpin) f amily which contain a flexible reactive site loop that interacts with, and is cleaved by the target proteinase. In cleaved and latent serpin s, the reactive site loop is inserted into a large central beta-sheet in the same molecule, whereas in ovalbumin, a nonfunctional serpin, th e reactive site loop is completely exposed and in an alpha-heliacal co nformation. however in neither conformation can the reactive site loop bind to target proteinases. here we report the structure of an intact and cleaved human antithrombin complex. The intact reactive site loop is in a novel conformation that seems well suited for interaction wit h proteinases such as thrombin and blood coagulation factor Xa.