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Members of the serine protease inhibitor (serpin) superfamily play import-ant roles in the inhibition of serine proteases involved in complex systems. This is evident in the regulation of coagulation serine proteases, especially the central enzyme in this system, thrombin. This review focuses on three serpins which are known to be key players in the regulation of thrombin: antithrombin and heparin cofactor II, which inhibit thrombin in its pro-coagulant role, and protein C inhibitor, which primarily inhibits the throm-bin⁄thrombomodulin complex, where thrombin plays an anticoagulant role. . | iFEBS Journal MINIREVIEW Control of the coagulation system by serpins Getting by with a little help from glycosaminoglycans Robert N. Pike1 2 Ashley M. Buckle1 2 Bernard F. le Bonniec3 and Frank C. Church4 1 Department of Biochemistry Molecular Biology and Co-operative Research Centres for Vaccine Technology and OralHealth Sciences Monash University Clayton Victoria Australia 2 The Victorian Bioinformatics Consortium Monash University Clayton Victoria Australia 3 INSERM U428 Faculte de Pharmacie Universite Paris V Paris France 4 Departments of Pathology and Laboratory Medicine Pharmacology and Medicine Carolina Cardiovascular Biology Center The University of North Carolina at Chapel Hill Schoolof Medicine NC USA Keywords antithrombin coagulation glycosaminoglycans heparin cofactor II proteases protein C inhibitor serpins thrombin Correspondence R. N. Pike Department of Biochemistry Molecular Biology Monash University Clayton Victoria 3800 Australia Fax 61 3 99054699 Tel 61 3 99053923 E-mail rob.pike@med.monash.edu.au Received 16 December 2004 accepted 14 July 2005 doi 10.1111 j.1742-4658.2005.04880.x Members of the serine protease inhibitor serpin superfamily play important roles in the inhibition of serine proteases involved in complex systems. This is evident in the regulation of coagulation serine proteases especially the central enzyme in this system thrombin. This review focuses on three serpins which are known to be key players in the regulation of thrombin antithrombin and heparin cofactor II which inhibit thrombin in its procoagulant role and protein C inhibitor which primarily inhibits the throm-bin thrombomodulin complex where thrombin plays an anticoagulant role. Several structures have been published in the past few years which have given great insight into the mechanism of action of these serpins and have significantly added to a wealth of biochemical and biophysical studies carried out previously. A major feature of these serpins is that they are .