RNA aptamer to thrombin binds anion-binding exosite-2 and alters protease inhibition by heparin-binding serpins.
FEBS Lett
; 568(1-3): 10-4, 2004 Jun 18.
Article
en En
| MEDLINE
| ID: mdl-15196911
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.
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Banco de datos:
MEDLINE
Asunto principal:
ARN
/
Heparina
/
Trombina
/
Cofactor II de Heparina
/
Antitrombinas
/
Inhibidor de Proteína C
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2004
Tipo del documento:
Article