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Title

Insights from the docking and molecular dynamics simulation of the Phosphopantetheinyl transferase (PptT) structural model from Mycobacterium tuberculosis

 

Authors

Karunakaran Rohini1* & Padmalayam Sadanandan Srikumar2

 

Affiliation

1Unit of Biochemistry, Faculty of Medicine, AIMST University, Bedong, Kedah, Malaysia; 2Unit of Psychiatry, Faculty of Medicine, AIMST University, Bedong, Kedah, Malaysia

 

Email

rohinik23@gmail.com; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received June 10, 2013; Accepted June 10, 2013; Published July 17, 2013

 

Abstract

A great challenge is posed to the treatment of tuberculosis due to the evolution of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis in recent times. The complex cell envelope of the bacterium contains unusual structures of lipids which protects the bacterium from host enzymes and escape immune response. To overcome the drug resistance, targeting “drug targets” which have a critical role in growth and virulence factor is a novel approach for better tuberculosis treatment. The enzyme Phosphopantetheinyl transferase (PptT) is an attractive drug target as it is primarily involved in post translational modification of various types-I polyketide synthases and assembly of mycobactin, which is required for lipid virulence factors. Our in silico studies reported that the structural model of M.tuberculosis PptT characterizes the structure-function activity. The refinement of the model was carried out with molecular dynamics simulations and was analyzed with root mean square deviation (RMSD), and radius of gyration (Rg). This confirmed the structural behavior of PptT in dynamic system. Molecular docking with substrate coenzyme A (CoA) identified the binding pocket and key residues His93, Asp114 and Arg169 involved in PptT-CoA binding. In conclusion, our results show that the M.tuberculosis PptT model and critical CoA binding pocket initiate the inhibitor design of PptT towards tuberculosis treatment.

 

Keywords

PptT, Mycobacterium tuberculosis, I-TASSER, Molecular dynamics simulations.

 

Citation

Rohini & Srikumar,   Bioinformation 9(13): 685-689 (2013)

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.