Enolase binds to RnpA in competition with <scp>PNP</scp>ase in <i>Staphylococcus aureus</i>

Wang, Xuejing; Chen, YangQuan; Wu, Minghao; Tian, Tian; Cheng, Tianyuan; Zhang, Xuan; Zang, Jianye

doi:10.1002/1873-3468.12859

Cited by 16 publications

(9 citation statements)

References 34 publications

(51 reference statements)

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“…To better understand the binding modes of the prepared naphthoquinone analogues (5 b, 5 j, and 5 q), a docking model was created using the crystal structure of the S. aureus PNPase catalytic domain (PDB ID: 5XEX). [43] Prior to molecular docking, the crystal structure of S. aureus receptor was prepared using the protein preparation wizard in Schrödinger Maestro (version 8.5, Schrödinger, LLC, New York, 2010). The crystal structure was downloaded from the protein data bank (PDB), and the chemical structures of the compounds were sketched using ChemDraw professional 15.1.…”

Section: In Silico Molecular Docking Studymentioning

confidence: 99%

Synthesis and Antimicrobial Evaluation of 1,4‐Naphthoquinone Derivatives as Potential Antibacterial Agents

Ravichandiran

Masłyk

Sheet³

et al. 2019

ChemistryOpen

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1,4‐Naphthoquinones are an important class of compounds present in a number of natural products. In this study, a new series of 1,4‐naphthoquinone derivatives were synthesized. All the synthesized compounds were tested for in vitro antimicrobial activity. In this present investigation, two Gram‐positive and five Gram‐negative bacterial strains and one pathogenic yeast strain were used to determine the antibacterial activity. Naphthoquinones tested for its antibacterial potencies, among seven of them displayed better antimicrobial activity against Staphylococcus aureus ( S. aureus ; 30–70 μg/mL). Some of the tested compounds showed moderate to low antimicrobial activity against Pseudomonas aeruginosa ( P. aeruginosa ) and Salmonella bongori ( S. bongori ; 70–150 μg/mL). In addition, most active compounds against S. aureus were evaluated for toxicity to human blood cells using a hemolysis assay. For better understanding, reactive oxygen species (ROS) generation, time‐kill kinetic study, and apoptosis, necrosis responses were investigated for three representative compounds.

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Section: In Silico Molecular Docking Studymentioning

confidence: 99%

Synthesis and Antimicrobial Evaluation of 1,4‐Naphthoquinone Derivatives as Potential Antibacterial Agents

Ravichandiran

Masłyk

Sheet³

et al. 2019

ChemistryOpen

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“…In this study, the RnpA knockdown system was developed using the synthetic regulatory small RNA system [ 20 ] since the RnpA protein, which is essential for cell viability, was reported to degrade mRNAs in vitro. [ 71 ] When introduced to a recombinant E. coli strain expressing the fluorescent mCherry protein, the RnpA knockdown system significantly increased the fluorescence intensity as well as the mCherry protein level while overexpression of rnpA decreased both the fluorescence intensity and the mCherry protein level. The general applicability of the RnpA knockdown system was also demonstrated by examining its positive effects on protein overproduction in 14 different E. coli strains.…”

Section: Discussionmentioning

confidence: 99%

Enhanced production of difficult‐to‐express proteins through knocking down rnpA gene expression

Chung

Kim

Lee

et al. 2023

Biotechnology Journal

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Escherichia coli has been employed as a workhorse for the efficient production of recombinant proteins. However, some proteins were found to be difficult to produce in E. coli. The stability of mRNA has been considered as one of the important factors affecting recombinant protein production. Here we report a generally applicable and simple strategy for enhancing mRNA stability, and consequently improving recombinant protein production in E. coli. RNase P, a ribozyme comprising an RNA subunit (RnpB) and a protein subunit (RnpA), is involved in tRNA maturation. Based on the finding that purified RnpA can digest rRNA and mRNA in vitro, it was reasoned that knocking down the level of RnpA might enhance recombinant protein production. For this, the synthetic small regulatory RNA‐based knockdown system was applied to reduce the expression level of RnpA. The developed RnpA knockdown system allowed successful overexpression of 23 different recombinant proteins of various origins and sizes, including Cas9 protein, antibody fragment, and spider silk protein. Notably, a 284.9‐kDa ultra‐high molecular weight, highly repetitive glycine‐rich spider silk protein, which is one of the most difficult proteins to produce, could be produced to 1.38 g L−1, about two‐fold higher than the highest value previously achieved, by a fed‐batch culture of recombinant E. coli strain employing the RnpA knockdown system. The RnpA‐knockdown strategy reported here will be generally useful for the production of recombinant proteins including those that have been difficult to produce.

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“…aureus, and others have also targeted the thioredoxin system . Polynucleotide phosphorylase (PNPase) is a bifunctional exoribonuclease responsible for mRNA turnover by dismantling the RNA chain starting at the 3′ end and working toward the 5′ end and synthesizing long, highly heteropolymeric tails in vivo . It acts as quality control for rRNA precursors in several bacteria, including S.…”

Section: Introductionmentioning

confidence: 99%

“… 23 Polynucleotide phosphorylase (PNPase) is a bifunctional exoribonuclease responsible for mRNA turnover by dismantling the RNA chain starting at the 3′ end and working toward the 5′ end and synthesizing long, highly heteropolymeric tails in vivo . 24 It acts as quality control for rRNA precursors in several bacteria, including S. aureus . We retrieved these proteins from the AlphaFold database for S. aureus (strain MRSA252) to perform molecular docking studies for our compounds since they have been reported to play a significant role in the survival of our target microorganisms.…”

Section: Introductionmentioning

confidence: 99%

Aminated Quinolinequinones as Privileged Scaffolds for Antibacterial Agents: Synthesis, In Vitro Evaluation, and Putative Mode of Action

et al. 2022

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Our previous studies have revealed that the aminated 1,4-quinone scaffold can be used for the development of novel antibacterial and/or antifungal agents. In this study, the aminated quinolinequinones (AQQ1−9) were designed, synthesized, and evaluated for their antimicrobial activity against a panel of seven bacterial strains (three Gram-positive and four Gramnegative bacteria) and three fungal strains. The structure−activity relationship (SAR) for the QQs was also summarized. The antibacterial activity results indicated that the two aminated QQs (AQQ6 and AQQ9) were active against Enterococcus faecalis (ATCC 29212) with a MIC value of 78.12 μg/mL. Besides, the two aminated QQs (AQQ8 and AQQ9) were active against Staphylococcus aureus (ATCC 29213) with MIC values of 4.88 and 2.44 μg/mL, respectively. The most potent aminated QQs (AQQ8 and AQQ9) were identified as promising lead molecules to further explore their mode of action. The selected QQs (AQQ8 and AQQ9) were further evaluated in vitro to assess their potential antimicrobial activity against each of 20 clinically obtained methicillin-resistant S. aureus isolates, antibiofilm activity, and bactericidal activity using time-kill curve assay. We found that the molecules prevented adhesion of over 50% of the cells in the biofilm. Molecular docking studies were performed to predict the predominant binding mode(s) of the ligands. We believe that the molecules need further investigation, especially against infections involving biofilm-forming microbes.

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Enolase binds to RnpA in competition with PNPase in Staphylococcus aureus

Cited by 16 publications

References 34 publications

Synthesis and Antimicrobial Evaluation of 1,4‐Naphthoquinone Derivatives as Potential Antibacterial Agents

Synthesis and Antimicrobial Evaluation of 1,4‐Naphthoquinone Derivatives as Potential Antibacterial Agents

Enhanced production of difficult‐to‐express proteins through knocking down rnpA gene expression

Aminated Quinolinequinones as Privileged Scaffolds for Antibacterial Agents: Synthesis, In Vitro Evaluation, and Putative Mode of Action

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