Structural and inhibition analysis of novel sulfur-rich 2-mercaptobenzothiazole and 1,2,3-triazole ligands against Mycobacterium tuberculosis DprE1 enzyme

  • Sumita Karan
  • Vipin K. Kashyap
  • Syed Shafi
  • Ajay K. SaxenaEmail author
Original Paper


Mycobacterium tuberculosis decaprenylphosphoryl-β-d-ribose oxidase (MtbDprE1) acts in concert with decaprenylphosphoryl-β-d-ribose 2-epimerase (MtbDprE2) and catalyzes the epimerization of DPR into DPA. DPA is the sole precursor for synthesis of arabinogalactan and lipoarabinomannan in the mycobacterial cell wall. MtbDprE1 is a unique antimalarial drug target and many covalent and non-covalent inhibitors against MtbDprE1 have been studied for their antituberculosis activities. In the current study, we have purified MtbDprE1 enzyme and synthesized six sulfur-rich 2-mercaptobenzothiazole and 1, 2, 3-triazole conjugated ligands and performed binding analysis with MtbDprE1. All ligands have shown competitive binding, as observed for other covalently and noncovalently bound MtbDprE1 inhibitors. Molecular docking analysis of six ligands with MtbDprE1 shows that they occupy the substrate binding pocket of MtbDprE1 and are stabilized by hydrogen bonds and van der Waals interactions. Our study shows that sulfur-rich 2-mercaptobenzothiazole ligands act as specific inhibitors against MtbDprE1 and could be used as antituberculosis agents.


Mycobacterial cell wall synthesis enzyme In vitro MtbDprE1-FAD ~ ligand binding In silico MtbDprE1-FAD-ligand structure 



Funding for the current work was supported by a grant from the Department of Biotechnology (No. PAC-SLS-AKS-DBT-01131216-737) to Ajay K Saxena. Partial funding from UGC resource networking, DST–PURSE, and UPE-II grants from Jawaharlal Nehru University are gratefully acknowledged. Sumita Karan and Vipin K. Kashyap were supported by UGC-NET research fellowship. The authors thank Amarjeet Kumar, Prof. N. SubbaRao’s student, who helped tremendously in docking analysis of these compounds. The authors thank AIRF facility of JNU for conducting the surface plasmon resonance experiment.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

894_2017_3403_MOESM1_ESM.pdf (42 kb)
Supplementary Fig. 1 Secondary structure assignment and sequence alignment of MtbDprE1 from related mycobacterial species. All DprE1 sequences are aligned using MultiAln program (Multiple sequence alignment with hierarchical clustering “F. CORPET,1988, Nucl. Acids Res., 16 (22), 10,881–10,890) and formatted using Espript3 program (Robert, X. and Gouet, P. (2014) “Deciphering the key features in protein structures with new ENDscript server” Nucl. Acids Res. 42(W1),W320-W324. (PDF 41 kb).


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Sumita Karan
    • 1
  • Vipin K. Kashyap
    • 1
  • Syed Shafi
    • 2
  • Ajay K. Saxena
    • 1
    Email author
  1. 1.Structural Biology Lab, School of Life SciencesJawaharlal Nehru UniversityNew DelhiIndia
  2. 2.Department of Chemistry, Faculty of ScienceJamia HamdardNew DelhiIndia

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