Computational studies on molecular interactions of 6-thioguanosine analogs with anthrax toxin receptor 1
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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 (C11H13N3O5). The data presented here strongly indicate that the interactions of these four residues are necessary for a stronger binding of the ATR1 with C11H13N3O5. Also, the study proposed C11H13N3O5 as an effective inhibitor by the comparison of docking energy.
Key wordsBacillus anthracis anthrax toxin receptor homology modelling 6-thiogunaosine analogs
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- Brunger, A. 1992. X-PLOR, Version 3.1: A System for X-Ray Crystallography and NMR. Yale University, New Haven, CT.Google Scholar
- James, M.M., John, E.D., John, H.C., Stephen, F.M. 2011. Protien-ligand interactions: Thermodynamics effects associated with increasing nonpolar surface area. JACS 133, 18515–18521.Google Scholar
- Mackerell, A.D. Jr., Bashford, D., Bellott, M., Dunbrack, R.L. Jr., Evanseck, J.D., Field, M.J., Fischer, S., Gao, J., Guo, H., Ha, S., Joseph-McCarthy, D., Kuchnir, L., Kuczera, K., Lau, F.T.K., Mattos, C., Michnick, S., Ngo, T., Nguyen, D.T., Prodhom, B., Reiher, W.E., Roux, B., Schlenkrich, M., Smith, J.C., Stote, R., Straub, J.E., Watanabe, M., Wiokiewicz-Kuczera, J., Yin, D., Karplus, M. 1998. All hydrogen empricial potential for molecular modeling and dynamic was studies of protein using the CHARMM22 force field. J Phys Chem 281, 1630–1635.Google Scholar
- Monique, A., Raynal, C.S., Adel, M.N., Ludmyl, A., Jurgen, B., Ernesto, A.S. 2007. Identification of an in vivo inhibitor of Bacillus anthracis spore germination. J Biol Chem 282, 12112–12118.Google Scholar
- Ramamoorthy, M., Chinnaiah, S.V., Maruthamuthu, R., Ekambaram, R. 2008. A study of molecular modeling, dynamics and mechanics of cyp2b6 and nk binding using Hex. JCIB 1, 109–114.Google Scholar