@article { author = {Ahmadi, Azam and Nazari, Raziyeh and Arjomandzadegan, Mohammad and Zolfaghari, Mohammad Reza and Vahidi, Vahideh and Poolad, Toktam and Kahbazi, Manijeh and Sadrnia, Maryam and Tousheh, Mojtaba and Rafiee, Pourya}, title = {nsights into Pyrazinamidase and DNA Gyrase Protein Structures in Resistant and Susceptible Clinical Isolates of Mycobacterium tuberculosis}, journal = {TANAFFOS (Respiration)}, volume = {15}, number = {3}, pages = {147-153}, year = {2016}, publisher = {National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran}, issn = {1735-0344}, eissn = {2345-3729}, doi = {}, abstract = {Background: Mutations in pncA and gyrA genes cause pyrazinamide (PZA) and fluroquinolone resistance in Mycobacterium tuberculosis (MTB). In the present study, structures of pyrazinamidase (PZase) and DNA gyrase proteins were studied in resistant and susceptible clinical isolates of MTB. Materials and Methods: Sixty clinical isolates of MTB were used in this study. Polymerase chain reaction (PCR) amplification of pncA and gyrA genes was accomplished on purified DNA. Sequence of the fragments was determined by an Applied Biosystems TM apparatus. Bioinformatic analysis was performed by online software and three-dimensional (3D) structures of proteins was predicted using Molegro Virtual Docker (MVD) Modeler software. Results: Amplified 744 and 194 bp fragments of pncA and gyrA genes, respectively were yielded suitable sequence results. Predicted 3D structures of proteins showed some differences between wild-type and mutant structures. Mutation in amino acid No.31 (T92C) caused an increase in distance from metal ion position to enzyme active site, but it was considered as a polymorphism. Docking results by MVD revealed a relationship in quinolone resistancedetermining regions (QRDR) amino acids in interaction with antibiotic. T92C mutation in PZase from non-polar aliphatic amino acid Ile (ATC) to polar aliphatic amino acid threonine (ACC) was a polymorphism. Conclusion: Structural changes in two important proteins related to drug resistance were proven in clinical isolates of MTB.}, keywords = {Mycobacterium tuberculosis,Pyrazinamidase,DNA Gyrase,Protein}, url = {https://www.tanaffosjournal.ir/article_240218.html}, eprint = {https://www.tanaffosjournal.ir/article_240218_6257688657a48d01ac2db6777abc8be8.pdf} }