scholarly journals Novel synthetic molecules targeting the bacterial RNA polymerase assembly

2005 ◽  
Vol 57 (2) ◽  
pp. 245-251 ◽  
Author(s):  
Estelle André ◽  
Lionel Bastide ◽  
Sylvie Michaux-Charachon ◽  
Anne Gouby ◽  
Philippe Villain-Guillot ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Bacterial Rna ◽  
Synthetic Molecules

Computer-aided structural and molecular insights into the mechanisms by which Pseudouridimycin (PUM) disrupts cleft extension in bacterial RNA polymerase to block DNA entry and exit

2020 ◽  
Vol 17 ◽  
Author(s):  
Ali H. Rabbad ◽  
Fisayo A. Olotu ◽  
Mahmoud E. Soliman
Keyword(s):  
Rna Polymerase ◽  
Bacterial Infections ◽  
Entry And Exit ◽  
Dynamic Binding ◽  
Binding Behavior ◽  
Bacterial Rna ◽  
Nucleotide Addition ◽  
Switch Regions ◽  
Cleft Extension ◽  
Key Residues

Background: The ability of Pseudouridimycin (PUM) to occupy the nucleotide addition site of bacterial RNA Polymerase (RNAP) underlies its inhibitory potency as previously reported. PUM has gained high research interest as a broad-spectrum nucleoside analog that has demonstrated exciting potentials in treating drug-resistant bacterial infections. Objective: Herein, we identified, for the first time, a novel complementary mechanism by which PUM elicits its inhibitory effects on bacterial RNAP. Methods: The dynamic binding behavior of PUM to bacterial RNAP was studied using various dynamic analyses approaches. Results and Discussion: Findings revealed that in addition to occupying the nucleotide addition site, PUM also interrupts the unimpeded entry and exit of DNA by reducing the mechanistic extension of the RNAP cleft and perturbing the primary conformations of the switch regions. Moreover, PUM binding reduced the distances between key residues in the β and β’ subunits that extend to accommodate the DNA. Conclusion: This study’s findings present structural insights that would contribute to the structure-based design of potent and selective PUM inhibitors.

scholarly journals Universal functions of the σ finger in alternative σ factors during transcription initiation by bacterial RNA polymerase

RNA Biology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Anastasiya Oguienko ◽  
Ivan Petushkov ◽  
Danil Pupov ◽  
Daria Esyunina ◽  
Andrey Kulbachinskiy
Keyword(s):  
Rna Polymerase ◽  
Transcription Initiation ◽  
Universal Functions ◽  
Bacterial Rna
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