Strawberry Dioxygenase: Vorapaxar A model for Antiplatelet Therapy

Abstract

A dioxygenase is an enzyme which incorporates both the atoms of molecular oxygen into kinds of substrate, undergoing various types of mechanisms. One of the most important functions of dioxygenases could be the cleavage of aromatic ring compounds, which play key roles in the degradation of aromatic compounds. Tissue factor (TF) is the membrane receptor that initiates coagulation pathway and it promotes developmental and tumor angiogenesis. The gut microbiota promotes TF-glycosylation and activation of coagulation protease. The anti-TF therapy reduces microbiota induced vascular remodeling and expression of the proangiogenic factor angiopoietin 1 (Ang-1) in the small intestine. Here, we report the Protease activated receptor PAR-1 antagonist Vorapaxar binding with the dioxygenase. The structure model suggests that how a highly lipophilic substrate can interact with the membrane integrated protein such as dioxygenase. Dioxygenase can be an important target for drug development for combinatorial drug therapy. The structure model reported here will aid the development of improved PAR-1 antagonist and also improve the understanding of Vorapaxar mode of actions and will justify its use for treatments of intracranial hemorrhages, coronary vascularization and peripheral arterial disease (PAD). We anticipate the structure model will also aid to the structure aided drug designing.