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image of Designing Novel Antibiotics against Pseudomonas aeruginosa to Tackle Antimicrobial Drug Resistance: Structure-based Drug Design of Inhibitors of t-RNA Methyltransferases (trmA) from Pseudomonas aeruginosa

Abstract

Introduction

The global rise in antibiotic resistance among pathogenic bacteria poses a critical threat to public health. , a Gram-negative opportunistic pathogen, displays both intrinsic and acquired resistance mechanisms. Emerging evidence implicates post-transcriptional tRNA modifications in antibiotic resistance, positioning tRNA-modifying enzymes like trmA as potential therapeutic targets.

Objective

This study aims to identify potential inhibitors of trmA to disrupt essential cellular pro- cesses and counter antibiotic resistance.

Methods

We employed a structure-based virtual screening strategy to identify compounds structurally analogous to S-adenosylmethionine, a universal methyl group donor and known trmA binder. Top-ranked compounds were further evaluated through molecular dynamics (MD) simulations to examine binding-induced conformational dynamics and stability.

Results

Compound 24762163 emerged as a lead candidate with favorable binding affinity and structural compatibility, as confirmed through docking and MD simulations. The compound formed stable interactions with the active site of trmA, indicating its inhibitory potential.

Discussion

The computational findings suggest that compound 24762163 may effectively disrupt trmA function, thereby impairing tRNA methylation and hindering protein synthesis in . Given the essential role of tRNA modifications in bacterial survival and resistance, targeting trmA represents a promising strategy for novel antimicrobial development.

Conclusion

This study identifies compound 24762163 as a promising trmA inhibitor and a potential therapeutic agent to counter antibiotic resistance in . Targeting tRNA-modifying methyltransferases may offer a novel approach in the fight against drug-resistant pathogens.

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2025-05-26
2025-09-10

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Designing Novel Antibiotics against Pseudomonas aeruginosa to Tackle Antimicrobial Drug Resistance: Structure-based Drug Design of Inhibitors of t-RNA Methyltransferases (trmA) from Pseudomonas aeruginosa
Bentham Science Publishers ; https://doi.org/10.2174/0122127968379517250519053237
/content/journals/ccb/10.2174/0122127968379517250519053237
/content/journals/ccb/10.2174/0122127968379517250519053237
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  • Article Type:     Research Article
Keywords: antibiotic resistance ; drug design ; tRNA modification ; tRNA methyltransferases ; molecular dynamics simulation ; enzyme inhibitor

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