Elucidating pyrazinamide resistance in M ycobacterium tuberculosis by molecular docking.

Unissa, A.N.; Sudha, S.; Selvakumar, N.

International Journal of Applied Biology and Pharmaceutical Technology; 2011; 2; 19-29.             

Abstract: Pyrazinamide, PZA - an important drug in the anti-tuberculosis therapy, activated by an enzyme Pyrazinamidase, PZase. The basis of PZA resistance in Mycobacterium tuberculosis is owing to mutation in pncA gene coding for PZase. The identification of the structural or functional defects in the mutant enzymes leading to resistance still remains an area to be explored. In the light of which, in the present study, the Wild-type and five mutant models Asp8Gly, Lys96Thr, Ser104Arg, Cys138Ser and Cys138Tyr were docked with PZA and its derivatives. Docking results predicts the compounds-10 and 4 were the good derivatives of PZA to bind with mutants of PZase. These models represent the first in-silico evidence for the binding interaction of PZase with PZA derivatives and analogues. The models may provide useful insights for designing new anti-TB agents in order to overcome the resistance developed with PZA .

Keywords: Mycobacterium tuberculosis, PZase, PZA resistance, Mutants, Derivatives, Docking

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