The first small-molecule inhibitors of members of the ribonuclease E family

Research output: Contribution to journalArticle

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The first small-molecule inhibitors of members of the ribonuclease E family. / Kime, Louise; Vincent, Helen A.; Gendoo, Deena; Jourdan, Stefanie S.; Fishwick, Colin W. G.; Callaghan, Anastasia J.; McDowall, Kenneth J.

In: Scientific Reports, Vol. 5, 8028, 26.01.2015.

Research output: Contribution to journalArticle

Harvard

Kime, L, Vincent, HA, Gendoo, D, Jourdan, SS, Fishwick, CWG, Callaghan, AJ & McDowall, KJ 2015, 'The first small-molecule inhibitors of members of the ribonuclease E family', Scientific Reports, vol. 5, 8028. https://doi.org/10.1038/srep08028

APA

Kime, L., Vincent, H. A., Gendoo, D., Jourdan, S. S., Fishwick, C. W. G., Callaghan, A. J., & McDowall, K. J. (2015). The first small-molecule inhibitors of members of the ribonuclease E family. Scientific Reports, 5, [8028]. https://doi.org/10.1038/srep08028

Vancouver

Kime L, Vincent HA, Gendoo D, Jourdan SS, Fishwick CWG, Callaghan AJ et al. The first small-molecule inhibitors of members of the ribonuclease E family. Scientific Reports. 2015 Jan 26;5. 8028. https://doi.org/10.1038/srep08028

Author

Kime, Louise ; Vincent, Helen A. ; Gendoo, Deena ; Jourdan, Stefanie S. ; Fishwick, Colin W. G. ; Callaghan, Anastasia J. ; McDowall, Kenneth J. / The first small-molecule inhibitors of members of the ribonuclease E family. In: Scientific Reports. 2015 ; Vol. 5.

Bibtex

@article{491a62dfdb03488a9f41b8380eb8a6a0,
title = "The first small-molecule inhibitors of members of the ribonuclease E family",
abstract = "The Escherichia coli endoribonuclease RNase E is central to the processing and degradation of all types of RNA and as such is a pleotropic regulator of gene expression. It is essential for growth and was one of the first examples of an endonuclease that can recognise the 5′-monophosphorylated ends of RNA thereby increasing the efficiency of many cleavages. Homologues of RNase E can be found in many bacterial families including important pathogens, but no homologues have been identified in humans or animals. RNase E represents a potential target for the development of new antibiotics to combat the growing number of bacteria that are resistant to antibiotics in use currently. Potent small molecule inhibitors that bind the active site of essential enzymes are proving to be a source of potential drug leads and tools to dissect function through chemical genetics. Here we report the use of virtual high-throughput screening to obtain small molecules predicted to bind at sites in the N-terminal catalytic half of RNase E. We show that these compounds are able to bind with specificity and inhibit catalysis of Escherichia coli and Mycobacterium tuberculosis RNase E and also inhibit the activity of RNase G, a paralogue of RNase E.",
author = "Louise Kime and Vincent, {Helen A.} and Deena Gendoo and Jourdan, {Stefanie S.} and Fishwick, {Colin W. G.} and Callaghan, {Anastasia J.} and McDowall, {Kenneth J.}",
year = "2015",
month = jan
day = "26",
doi = "10.1038/srep08028",
language = "English",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - The first small-molecule inhibitors of members of the ribonuclease E family

AU - Kime, Louise

AU - Vincent, Helen A.

AU - Gendoo, Deena

AU - Jourdan, Stefanie S.

AU - Fishwick, Colin W. G.

AU - Callaghan, Anastasia J.

AU - McDowall, Kenneth J.

PY - 2015/1/26

Y1 - 2015/1/26

N2 - The Escherichia coli endoribonuclease RNase E is central to the processing and degradation of all types of RNA and as such is a pleotropic regulator of gene expression. It is essential for growth and was one of the first examples of an endonuclease that can recognise the 5′-monophosphorylated ends of RNA thereby increasing the efficiency of many cleavages. Homologues of RNase E can be found in many bacterial families including important pathogens, but no homologues have been identified in humans or animals. RNase E represents a potential target for the development of new antibiotics to combat the growing number of bacteria that are resistant to antibiotics in use currently. Potent small molecule inhibitors that bind the active site of essential enzymes are proving to be a source of potential drug leads and tools to dissect function through chemical genetics. Here we report the use of virtual high-throughput screening to obtain small molecules predicted to bind at sites in the N-terminal catalytic half of RNase E. We show that these compounds are able to bind with specificity and inhibit catalysis of Escherichia coli and Mycobacterium tuberculosis RNase E and also inhibit the activity of RNase G, a paralogue of RNase E.

AB - The Escherichia coli endoribonuclease RNase E is central to the processing and degradation of all types of RNA and as such is a pleotropic regulator of gene expression. It is essential for growth and was one of the first examples of an endonuclease that can recognise the 5′-monophosphorylated ends of RNA thereby increasing the efficiency of many cleavages. Homologues of RNase E can be found in many bacterial families including important pathogens, but no homologues have been identified in humans or animals. RNase E represents a potential target for the development of new antibiotics to combat the growing number of bacteria that are resistant to antibiotics in use currently. Potent small molecule inhibitors that bind the active site of essential enzymes are proving to be a source of potential drug leads and tools to dissect function through chemical genetics. Here we report the use of virtual high-throughput screening to obtain small molecules predicted to bind at sites in the N-terminal catalytic half of RNase E. We show that these compounds are able to bind with specificity and inhibit catalysis of Escherichia coli and Mycobacterium tuberculosis RNase E and also inhibit the activity of RNase G, a paralogue of RNase E.

UR - http://europepmc.org/articles/PMC4500164

U2 - 10.1038/srep08028

DO - 10.1038/srep08028

M3 - Article

C2 - 26168261

VL - 5

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 8028

ER -