Title of article :
Allosteric activation of human α-thrombin through exosite 2 by suramin analogs
Author/Authors :
Cargnelutti، نويسنده , , Maria Thereza and Marques، نويسنده , , Adriana Fonseca and Esser، نويسنده , , Daniel and Monteiro، نويسنده , , Robson Q. and Kassack، نويسنده , , Matthias U. and Lima، نويسنده , , Luis Mauricio T.R.، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2012
Abstract :
Thrombin is a serine protease that plays fundamental roles in hemostasis. We have recently elucidated the crystal structure of thrombin in complex with suramin, evidencing the interaction through the anion binding exosite 2. Here, we show that the activity of thrombin toward natural and synthetic substrates is enhanced by suramin as well as analogs of suramin at a low micromolar range prior to an inhibitory component at higher concentrations. Suramin analogs substituted by phenyl and chlorine instead of methyl were the most efficient in promoting allosteric activation, with an enhancement of enzymatic activity of 250% and 630% respectively. We discuss the importance of exosite 2 as a regulatory site for ligands in both the procoagulant and inhibitory scenarios.
Keywords :
fibrinogen , thrombin , allosteric activation , Suramin , Exosite-2
Journal title :
Archives of Biochemistry and Biophysics
Journal title :
Archives of Biochemistry and Biophysics