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

Martha L. Jeter, Linda V. Ly, Yolanda M Fortenberry, Herbert C. Whinna, Rebekah R. White, Christopher P. Rusconi, Bruce A. Sullenger, Frank C. Church

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)10-14
Number of pages5
JournalFEBS Letters
Volume568
Issue number1-3
DOIs
StatePublished - Jun 18 2004
Externally publishedYes

Fingerprint

Nucleotide Aptamers
Serpins
Thrombin
Heparin Cofactor II
Anions
Heparin
Peptide Hydrolases
Protein C Inhibitor
Antithrombins
Binding Sites
Antithrombin Proteins
Glycosaminoglycans
Anticoagulants

Keywords

  • AT, antithrombin
  • exosite-1 and -2, anion-binding exosite-1 and anion-binding exosite-2
  • HCII, heparin cofactor II
  • Heparin
  • PCI, protein C inhibitor
  • RNA aptamer
  • Serpin
  • Serpin, serine protease inhibitor
  • Thrombin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

RNA aptamer to thrombin binds anion-binding exosite-2 and alters protease inhibition by heparin-binding serpins. / Jeter, Martha L.; Ly, Linda V.; Fortenberry, Yolanda M; Whinna, Herbert C.; White, Rebekah R.; Rusconi, Christopher P.; Sullenger, Bruce A.; Church, Frank C.

In: FEBS Letters, Vol. 568, No. 1-3, 18.06.2004, p. 10-14.

Research output: Contribution to journalArticle

Jeter, ML, Ly, LV, Fortenberry, YM, Whinna, HC, White, RR, Rusconi, CP, Sullenger, BA & Church, FC 2004, 'RNA aptamer to thrombin binds anion-binding exosite-2 and alters protease inhibition by heparin-binding serpins', FEBS Letters, vol. 568, no. 1-3, pp. 10-14. https://doi.org/10.1016/j.febslet.2004.04.087
Jeter, Martha L. ; Ly, Linda V. ; Fortenberry, Yolanda M ; Whinna, Herbert C. ; White, Rebekah R. ; Rusconi, Christopher P. ; Sullenger, Bruce A. ; Church, Frank C. / RNA aptamer to thrombin binds anion-binding exosite-2 and alters protease inhibition by heparin-binding serpins. In: FEBS Letters. 2004 ; Vol. 568, No. 1-3. pp. 10-14.
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AU - White, Rebekah R.

AU - Rusconi, Christopher P.

AU - Sullenger, Bruce A.

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KW - Thrombin

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