1H, 15N, 13C resonance assignments for pyrazinoic acid binding domain of ribosomal protein S1 from Mycobacterium tuberculosis

2016 ◽  
Vol 10 (2) ◽  
pp. 321-324 ◽  
Author(s):  
Biling Huang ◽  
Jinglin Fu ◽  
Chenyun Guo ◽  
Xueji Wu ◽  
Donghai Lin ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ribosomal Protein ◽  
Resonance Assignments ◽  
Binding Domain ◽  
Ribosomal Protein S1 ◽  
Pyrazinoic Acid

scholarly journals Mycobacterium tuberculosis ribosomal protein S1 (RpsA) and variants with truncated C-terminal end show absence of interaction with pyrazinoic acid

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Katherine Vallejos-Sánchez ◽  
Juan M. Lopez ◽  
Ricardo Antiparra ◽  
Emily Toscano ◽  
Harry Saavedra ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ribosomal Protein ◽  
Ribosomal Protein S1 ◽  
Pyrazinoic Acid

Discovery and evaluation of new compounds targeting ribosomal protein S1 in antibiotic-resistant Mycobacterium Tuberculosis

2020 ◽  
Vol 196 ◽  
pp. 112317
Author(s):  
Yazhuang Dai ◽  
Yinqiu Xu ◽  
Chenyun Guo ◽  
Xiaowen Xue ◽  
Donghai Lin ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ribosomal Protein ◽  
Antibiotic Resistant ◽  
Ribosomal Protein S1 ◽  
New Compounds

Solution structure and backbone dynamics for S1 domain of ribosomal protein S1 from Mycobacterium tuberculosis

2019 ◽  
Vol 48 (6) ◽  
pp. 491-501 ◽  
Author(s):  
Biling Huang ◽  
Shihui Fan ◽  
Yan Liu ◽  
Yufen Zhao ◽  
Donghai Lin ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ribosomal Protein ◽  
Solution Structure ◽  
Backbone Dynamics ◽  
Ribosomal Protein S1

Computational Insight into the Binding Mechanism of Pyrazinoic Acid to RpsA Protein

2021 ◽  
Vol 01 ◽  
Author(s):  
Ashfaq Ur Rehman ◽  
Sadat Ali ◽  
Humaira Rafiq ◽  
Salman Rasheed ◽  
Faisal Neuroz ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Ribosomal Protein ◽  
Resistance Mechanism ◽  
Binding Pocket ◽  
Dynamics Simulation ◽  
Drug Resistant ◽  
Wild Type ◽  
Ribosomal Protein S1 ◽  
Resistant Tuberculosis ◽  
Pyrazinoic Acid

Background: Resistance to the critical first line anti-tubercular drug, Pyrazinamide, is a significant obstacle to achieving the global end to tuberculosis targets. Approximately 50% of multidrug-resistant tuberculosis and over 90% of extensively drug-resistant tuberculosis strains are also Pyrazinamide resistant. Pyrazinamide is a pro-drug that reduce the duration of tuberculosis therapy time by 9-12 months, while used as an anti-biotic in the 1st- & 2nd-line tuberculosis treatment regimens. Pyrazinamidase is an enzyme, encoded by pncA gene, is responsible for the amide hydrolysis of Pyrazinamide into active Pyrazinoic acid. Pyrazinoic acid, could inhibit trans-translation by binding to Ribosomal protein S1 and competing with tmRNA, the natural cofactor of Ribosomal protein S1. Although pncA mutations have been commonly associated with Pyrazinamide resistance, a small number of resistance cases have been associated with mutations in Ribosomal protein S1. Ribosomal protein S1was recently identified as a possible target of Pyrazinamide based on its binding activity to Pyrazinoic acid and the capacity to inhibit trans-translation. Objective: Despite the critical role played by Pyrazinamide, its mechanisms of action are not yet fully understood. Therefore, an effort to explore the resistance mechanism toward Pyrazinamide drug in Mycobacterium (M.) tuberculosis. Methods: An extensive molecular dynamics simulation was performed using the AMBER software package. We mutated residues of the binding site (i.e., F307A, F310A, and R357A) in the RpsA S1 domain to address the drug-resistant mechanism of RpsA in complex that might be responsible for Pyrazinamide resistance. Moreover, it is challenging to collect the drug mutant combine complex of a protein by single-crystal X-ray diffraction. Thus, the total three structures were prepared by inducing mutations in the wild-type protein using PyMol. Results: The dynamics results revealed that mutation in binding pocket produced Pyrazinamide resistance due to the specificity of these residues in binding pockets which result in scarcity of hydrophobic and hydrogen bonding interaction with Pyrazinoic acid, which increases the CA-distance between the binding pocket residues as compared to wild type RpsA that lead to structural instability. Conclusion: The overall dynamic results will provide useful information behind the drug resistance mechanism to manage tuberculosis and also helps in better management for future drug resistance.

Chemical shift assignments of Ribosomal protein S1 from Mycobacterium tuberculosis

2017 ◽  
Vol 11 (2) ◽  
pp. 133-136 ◽  
Author(s):  
Jinglin Fu ◽  
Biling Huang ◽  
Donghai Lin ◽  
Xinli Liao
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Chemical Shift ◽  
Ribosomal Protein ◽  
Chemical Shift Assignments ◽  
Ribosomal Protein S1
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