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Construction of a plasminogen activator inhibitor‐1 variant without measurable affinity to vitronectin but otherwise normal
Author(s) -
Jensen Jan K,
Durand Michelle K.V,
Skeldal Sune,
Dupont Daniel M,
Bødker Julie S,
Wind Troels,
Andreasen Peter A
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01405-4
Subject(s) - vitronectin , chemistry , plasminogen activator , plasminogen activator inhibitor 1 , receptor , protease , microbiology and biotechnology , inhibitory postsynaptic potential , activator (genetics) , binding site , biochemistry , protease inhibitor (pharmacology) , integrin , biology , enzyme , genetics , endocrinology , virus , antiretroviral therapy , viral load
Vitronectin (VN) and plasminogen activator inhibitor‐1 (PAI‐1) have important functional interactions: VN stabilises the protease inhibitory activity of PAI‐1 and PAI‐1 inhibits binding of adhesion receptors to VN. Having previously mapped the PAI‐1 binding area for VN, we have now constructed a PAI‐1 variant, R103A‐M112A‐Q125A, without measurable affinity to VN, but with full protease inhibitory activity and endocytosis receptor binding. As a tool for evaluating the physiological and pathophysiological functions of the PAI‐1–VN interaction, our new variant is far superior to the previously widely used PAI‐1 variant Q125K, which we have found possesses an only about 10‐fold reduced affinity to VN.