Exploring the Pyrazinamide Drug Resistance Mechanism of Clinical Mutants T370P and W403G in Ribosomal Protein S1 of Mycobacterium tuberculosis

Journal of Chemical Information and Modeling
Ashfaq Ur RehmanHai-Feng Chen

Abstract

Pyrazinamide (PZA) is an essential first line antitubercular drug, which plays a crucial role in tuberculosis treatment. The PZA, which is considered as a pro-drug needs an enzyme of mycobacterial pyrazinamidase (PZase) for its conversion into an active form pyrazinoic acid. Further, this active form of PZA inhibits the ribosomal proteins S1, which facilitates the transfer-mRNA complex formation throughout the translation. The spontaneous mutations in RpsA have been found to be associated with PZA drug resistance. However, the drug resistance mechanism is still unclear. Furthermore, there is no such information available about the structural dynamics of RpsA protein because of mutations that confer Pyrazinoic acid resistance. Moreover, a total of 18 clinical PZA-resistant isolates were investigated and found to be pncAWT, which allowed exploration of the resistance mechanism of RpsA in the mutated state. Samples were repeated for the drug susceptibility testing followed by RpsA gene sequencing. A total of 11 clinical isolates harbored a total of 15 mutations. Almost half of the total strains (7/15) were observed to be in the conserved region of RpsA and known as Mycobacterium tuberculosis C-terminal domain. In the current study...Continue Reading

References

Jun 26, 2003·Nucleic Acids Research·T Andrew BinkowskiJie Liang
Aug 12, 2003·Journal of Molecular Biology·Gail J BartlettJanet M Thornton
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
May 19, 2004·Proceedings of the National Academy of Sciences of the United States of America·Trinh Xuan HoangAmos Maritan
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jun 28, 2005·Nucleic Acids Research·Dina Schneidman-DuhovnyHaim J Wolfson
Feb 17, 2007·Journal of the American Chemical Society·Hai-Feng Chen, Ray Luo
Nov 16, 2007·Proteins·Mickey Kosloff, Rachel Kolodny
Oct 28, 2008·Journal of Molecular Biology·Gia G MaisuradzeHarold A Scheraga
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Jul 17, 2009·Nucleic Acids Research·Philippe SalahFrançois Bontems
Sep 17, 2009·Nature Reviews. Molecular Cell Biology·Catherine L WorthTom L Blundell
Mar 9, 2010·Journal of Chemical Information and Modeling·Ryan G Coleman, Kim A Sharp
Jul 23, 2011·Methods in Molecular Biology·Chongmei Dong, Bing Yu
Dec 28, 2012·Journal of Clinical Microbiology·Sami O SimonsDick van Soolingen
Sep 25, 2015·Nucleic Acids Research·Sunghwan KimStephen H Bryant
Sep 10, 2013·Journal of Chemical Theory and Computation·Romelia Salomon-FerrerRoss C Walker
Aug 1, 2008·Journal of Chemical Theory and Computation·Hai-Feng Chen
Feb 1, 2012·Molecular Informatics·Nadine Homeyer, Holger Gohlke
Aug 12, 2016·The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·A B SutharA D Harries
Sep 21, 2017·Nature Communications·Adam N YadonAlexander S Pym
Oct 6, 2017·Journal of Cellular Biochemistry·Mansi AggarwalAbhinav Grover
Jan 18, 2018·Bioinformatics·Jaime Rodríguez-Guerra Pedregal, Jean-Didier Maréchal
Jun 20, 2018·The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·K FloydM Raviglione

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Citations

Sep 29, 2019·Marine Drugs·Muhammad Tahir KhanDong Qing Wei
Apr 25, 2020·Frontiers in Molecular Biosciences·Muhammad Tahir KhanDong-Qing Wei
Apr 24, 2020·Biotechnology Letters·Chuang YanGuimin Zhang
Jan 29, 2020·International Journal of Biological Macromolecules·Ashfaq Ur RehmanHai-Feng Chen
Mar 3, 2021·Molecular Diversity·Oluwatoyin BabatundeShahnaz Perveen
May 20, 2021·Physical Chemistry Chemical Physics : PCCP·Ashfaq Ur RehmanHai-Feng Chen
Jun 28, 2019·Journal of Chemical Information and Modeling·Ashfaq Ur RehmanHai-Feng Chen

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