RNA aptamer to thrombin binds anion-binding exosite-2 and alters protease inhibition by heparin-binding serpins.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Jeter, ML; Ly, LV; Fortenberry, YM; Whinna, HC; White, RR; Rusconi, CP; Sullenger, BA; Church, FC

Published Date

  • June 18, 2004

Published In

Volume / Issue

  • 568 / 1-3

Start / End Page

  • 10 - 14

PubMed ID

  • 15196911

Pubmed Central ID

  • 15196911

International Standard Serial Number (ISSN)

  • 0014-5793

Digital Object Identifier (DOI)

  • 10.1016/j.febslet.2004.04.087

Language

  • eng

Conference Location

  • England