The story of the serpin plasminogen activator inhibitor 1: is there any need for another mutant?
The importance of obtaining insight in the structure/function relationship in the serpin plasminogen activator inhibitor type-1 can be understood from the major role PAI-1 plays in different (patho)physiological processes, mainly because of its involvement in the plasminogen/plasmin system. Moreover, during the past years, studies indicated a contribution of PAI-1 to the development of cardiovascular disease in common syndromes such as atherosclerosis, diabetes and hypertension. Furthermore, PAI-1 also inhibits u-PA, attributing a role in phenomena such as cell migration and tissue remodelling. Considering the role of PAI-1 in such various pathogenic path-ways, detailed insight into the structure/function relationship in PAI-1 might provide a means of interfering with a given pathological situation without disturbing other physiological processes. Therefore, since the discovery of PAI-1 and the cloning of its cDNA 20 years ago, over 600 PAI-1 variants have been constructed, elucidating the most important structural features of PAI-1. This review gives an overview of the contribution of the different PAI-1 variants to the understanding of the structure/function relationship in PAI-1, based on the different functional features of PAI-1.
De Taeye
Bart
B
Laboratory of Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Gils
Ann
A
Declerck
Paul J
PJ
D000818:Animals; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors