Objective: Tb is considered to be growing menaces in various countries especially Africa and South East Asia. In 2011, 8.7 million people fell ill with TB, out of which a total of about 1.4 million people died. The children being affected in large, increases the severity of Tb. It remains to be the leading cause of death of people infected with HIV. The growing multidrug resistant strains of bacteria affecting the population has increase since 2010. The search for potential targets for fighting Tb has identified different pathways for drug development against tuberculosis. One such pathway identified, an enzyme alpha phosphoglucomutase involved in bacterial polysaccharide capsule formation, important for bacterial virulence and infection. The absence of X-ray crystallographic structure of alpha phosphoglucomutase resulted in the modelling of this potential target. Methods: Homology modelling of was performed by modeller9.1, the multiple sequence alignment was carried out selecting three different relevant templates. Model evaluation was performed using Ramachandran plot and ERRAT plot, further RMSD with the template obtained using Pymol. Results: Stereochemical evaluation of protein by Ramachandran plot indicated a good quality model with 99.8% residues in the most favoured and allowed regions. The model was compared with the suitable template by superimposing the structures, RMSD was determined to be 0.202Å, the further analysis by ERRAT program gave a score of 95.733, both indicating a good quality model. Conclusion: The various results obtained, conclude the reliability of modelled protein which can be further used for Denovo design of inhibitors against the target.
M. Mukesh, M Prathap, M., and Dr. Sabitha M., “Structural model of the alpha phosphoglucomutase: A promising target for the treatment of mycobacterium tuberculosis”, International Journal of Pharmacy and Pharmaceutical Sciences., vol. 5, no. 2, pp. 107-114, 2013.