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Inhibition of Klebsiella Pneumoniae DnaB Helicase by the Flavonol Galangin

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Abstract

Klebsiella pneumoniae is a ubiquitous opportunistic pathogen that colonizes at the mucosal surfaces in humans and causes severe diseases. Many clinical strains of K. pneumoniae are highly resistant to antibiotics. Here, we used fluorescence quenching to show that the flavonols galangin, myricetin, quercetin, and kaempferol, bearing different numbers of hydroxyl substituent on the aromatic rings, may inhibit dNTP binding of the primary replicative DnaB helicase of K. pneumoniae (KpDnaB), an essential component of the cellular replication machinery critical for bacterial survival. The binding affinity of KpDnaB to dNTPs varies in the following order: dCTP ~ dGTP > dTTP > dATP. Addition of 10 μM galangin significantly decreased the binding ability of KpDnaB to dATP, whereas the binding affinity of KpDnaB to dGTP that was almost unaffected. Our analyses suggest that these flavonol compounds may be used in the development of new antibiotics that target K. pneumoniae and other bacteria.

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Abbreviations

Kp :

Klebsiella pneumoniae

K d :

The dissociation constant

dsDNA:

Double-stranded DNA

ssDNA:

Single-stranded DNA

Myr:

Myricetin

Que:

Quercetin

Kae:

Kaempferol

Gal:

Galangin

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Acknowledgments

We thank Mr. Shun-Chuan Yang for constructing the pET21e-KpDnaB plasmid. This research was supported a grant from the National Research Program for Genome Medicine (NSC 99-3112-B-040-001 to C.Y. Huang).

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Authors and Affiliations

  1. Department of Biomedical Sciences, Chung Shan Medical University, No.110, Sec.1, Chien-Kuo N. Rd., Taichung, Taiwan

    Cheng-Chieh Chen & Cheng-Yang Huang

  2. Department of Medical Research, Chung Shan Medical University Hospital, No.110, Sec.1, Chien-Kuo N. Rd., Taichung, Taiwan

    Cheng-Yang Huang

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  1. Cheng-Chieh Chen
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  2. Cheng-Yang Huang
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Correspondence to Cheng-Yang Huang.

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Chen, CC., Huang, CY. Inhibition of Klebsiella Pneumoniae DnaB Helicase by the Flavonol Galangin. Protein J 30, 59–65 (2011). https://doi.org/10.1007/s10930-010-9302-0

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