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

  • Nitin K. Singh
  • Britto C. Pakkkianathan
  • Manish Kumar
  • Jayssima R. Daddam
  • Sridhar Jayavel
  • Mani Kannan
  • Girinath G. Pillai
  • Muthukalingan KrishnanEmail author


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 words

Bacillus anthracis anthrax toxin receptor homology modelling 6-thiogunaosine analogs 


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Copyright information

© International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Nitin K. Singh
    • 1
  • Britto C. Pakkkianathan
    • 1
  • Manish Kumar
    • 2
  • Jayssima R. Daddam
    • 3
  • Sridhar Jayavel
    • 4
  • Mani Kannan
    • 1
  • Girinath G. Pillai
    • 5
  • Muthukalingan Krishnan
    • 1
    Email author
  1. 1.Department of Environmental BiotechnologyBharathidasan UniversityTiruchirappalliIndia
  2. 2.Advanced Instrumentation Research FacilityJawaharlal Nehru UniversityNew DelhiIndia
  3. 3.Department of BioinformaticsGlobal Insitute of BiotechnologyHimayat NagaraIndia
  4. 4.UGC-Networking Resource Centre, School of Biological SciencesMadurai Kamaraj UniversityMaduraiIndia
  5. 5.Florida Center for Heterocyclic CompoundsUniversity of FloridaGainesvilleUSA

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