BACK TO CONTENTS   |    PDF   |    PREVIOUS   |    NEXT

Title

 

 

 

 

 

Insight to pyrazinamide resistance in Mycobacterium tuberculosis by molecular docking

 

Authors

 

A. Nusrath Unissa*, N. Selvakumar, Sameer Hassan

Affiliation

 

1Department of Mycobacteriology, Tuberculosis Research Centre (TRC), Indian Council of Medical Research (ICMR), Mayor V. R. Ramanathan Road, Chetput, Chennai 600 031, Tamil Nadu, India; 2Department of Mycobacteriology, TRC, ICMR; 3Department of Biomedical Informatics Centre, Indian Council of Medical Research (ICMR), Mayor V. R. Ramanathan Road, Chetput, Chennai 600 031, Tamil Nadu, India

 

Email

 

nusrathunissa@gmail.com

 

Article Type

 

Hypothesis

Date

 

Received April 09, 2009; Revised June 10, 2009; Accepted June 13, 2009; Published August 18, 2009

 

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 was owing to mutation in pncA gene coding for PZase. Homology modeling of PZase was performed using software Discovery Studio (DS) 2.0 based on the crystal structure of the PZase from Pyrococcus horikoshii (PDB code 1im5), in this study. The model comprises of one sheet with six parallel strands and seven helices with the amino acids Asp8, Asp49, Trp68, Lys96, Ala134, Thr135 and Cys138 at the active site. Five mutants were generated with Gly at position 8, Thr at position 96, Arg at position 104, Tyr and Ser at position 138. The Wild-type (WT) and five mutant models were docked with PZA. The results indicate that the mutants Lys96Thr, Ser104Arg Asp8Gly and Cys138Tyr may contribute high-level drug resistance than Cys138Ser. These models provide the first in-silico evidence for the binding interaction of PZA with PZase and form the basis for rationalization of PZA resistance in naturally occurring pncA mutant strains of M. tuberculosis.

 

Keywords

 

Mycobacterium tuberculosis, PZA resistance, PZase, mutants, docking

Citation

 

Unissa et al, Bioinformation 4(1): 24-29 (2009)

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.