Computational studies on molecular interactions of 6-thioguanosine analogs with anthrax toxin receptor 1

Dormant endospores of Bacillus anthracis are the causative agent of anthrax, which is an acute disease for both human and animals. Anthrax has been practised as biological weapon because of two attributes: i) short duration of spore germination, and ii) lethal toxaemia of the vegetative stage. Pathogenesis is caused by the activity of edema toxin and lethal toxin. Protective antigen (PA), is an essential component of both complexes, binds to Anthrax Toxin Receptor (ATR) and mediates the lethality in mammals. The combination of vaccine and antibiotics are preferred to be effective treatment for destruction of the vegetative cell wall but could not be a successive destructor for endospores. So the present study is intended to identify the small molecules as a potential inhibitor for ATR1. 3D structure of Anthrax Toxin Receptor 1 (ATR1) was built by using the crystal structure of Anthrax Toxin Receptor 2 (ATR2) from Homo sapiens as template. Molecular docking of 6-thiogunaosine (6-TG) analogs was performed on the ATR1 model and effective inhibitor was selected based on the docking results. The docking results showed that the three residues in the ATR1 binding pocket (Phe162, Asp160, and Phe22) were essential for making hydrogen bond with the 2-(2-bromo-6-chloro-4H-purin-9(5H)-yl)- 5-(hydroxymethyl) tetrahydrofuran-3,4-diol (C(11)H(13)N(3)O(5)). The data presented here strongly indicate that the interactions of these four residues are necessary for a stronger binding of the ATR1 with C(11)H(13)N(3)O(5). Also, the study proposed C(11)H(13)N(3)O(5) as an effective inhibitor by the comparison of docking energy.