Tyrosine sulfation modulates activity of tick-derived thrombin inhibitors

Tyrosine sulfation strongly enhances the inhibition of thrombin by the tick-derived anticoagulants madanin-1 and chimadanin. Protein chemical synthesis and structural studies have revealed a mode of inhibition that is unprecedented among cysteine-free anticoagulant proteins. This inhibition occurs through the recognition of the highly basic exosite II of thrombin.