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RNA aptamer to thrombin binds anion‐binding exosite‐2 and alters protease inhibition by heparin‐binding serpins
Author(s) -
Jeter Martha L,
Ly Linda V,
Fortenberry Yolanda M,
Whinna Herbert C,
White Rebekah R,
Rusconi Christopher P,
Sullenger Bruce A,
Church Frank C
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/j.febslet.2004.04.087
Subject(s) - thrombin , heparin cofactor ii , aptamer , chemistry , antithrombin , heparin , biochemistry , binding site , protease , serpin , microbiology and biotechnology , enzyme , biology , platelet , immunology , gene
We studied the RNA aptamer Toggle‐25/thrombin interaction during inhibition by antithrombin (AT), heparin cofactor II (HCII) and protein C inhibitor (PCI). Thrombin inhibition was reduced 3‐fold by Toggle‐25 for AT and HCII, but it was slightly enhanced for PCI. In the presence of glycosaminoglycans, AT and PCI had significantly reduced thrombin inhibition with Toggle‐25, but it was only reduced 3‐fold for HCII. This suggested that the primary effect of aptamer binding was through the heparin‐binding site of thrombin, anion‐binding exosite‐2 (exosite‐2). We localized the Toggle‐25 binding site to Arg 98, Glu 169, Lys 174, Asp 175, Arg 245, and Lys 248 of exosite‐2. We conclude that a RNA aptamer to thrombin exosite‐2 might provide an effective clinical reagent to control heparin's anticoagulant action.