title: Shape-shifting serpins--advantages of a mobile mechanism.
abstract: Serpins use an extraordinary mechanism of protease inhibition that depends on a rapid and marked conformational change and causes destruction of the covalently linked protease. Serpins thus provide stoichiometric, irreversible inhibition, and their dependence on conformational change is exploited for signalling and clearance. The regulatory advantages provided by structural mobility are best illustrated by the heparin activation mechanisms of the plasma serpins antithrombin and heparin cofactor II. This mechanistic complexity, however, renders serpins highly susceptible to disease-causing mutations. Recent crystal structures reveal the intricate conformational rearrangements involved in protease inhibition, activity modulation and the unique molecular pathology of the remarkable shape-shifting serpins.
authors.affiliation: University of Cambridge, Department of Haematology, Cambridge Institute for Medical Research, Division of Structural Medicine, Thrombosis Research Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 2XY, UK. jah52@cam.ac.uk
authors.forename: James A
authors.initials: JA
authors.lastname: Huntington
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000737:chemistry / Q000502:physiology; D015844:Heparin Cofactor II / Q000737:chemistry / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D015843:Serpins / Q000737:chemistry* / Q000502:physiology
chemical_list: D000991:Antithrombins; D015843:Serpins; D015844:Heparin Cofactor II; D012697:Serine Endopeptidases