Elucidating pyrazinamide resistance in mycobacterium tuberculosis by molecular docking.
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Date
2011-10
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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 (Mtb) 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. The Wild-type (WT) and five mutant models Asp8Gly,
Lys96Thr, Ser104Arg, Cys138Ser and Cys138Tyr were docked with PZA and its derivatives.
In the present study, docking results has aided in predicting the best form of PZA to bind with
mutants of PZase to be compounds-10 and 4. These models represent the first in-silico evidence
for the binding interaction of PZase with PZA derivatives/analogues. The models may provide
useful chemical insights for designing new anti-TB agents in order to overcome the resistance
developed with PZA.
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Keywords
Mycobacterium tuberculosis, PZase, PZA resistance, Mutants, Derivatives, Docking
Citation
Unissa A Nusrath, Sudha S, Selvakumar N. Elucidating pyrazinamide resistance in mycobacterium tuberculosis by molecular docking. International Journal of Applied Biology and Pharmaceutical Technology. 2011 Oct-Dec; 2(4): 19-29.