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Issue 49, 2018
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Protein–DNA complex-guided discovery of the antibacterial lead E1 for restoring the susceptibility of Klebsiella Pneumoniae to polymyxin B by targeting the response regulator PmrA

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Abstract

A new antibacterial drug is urgently needed. We employed a protein–DNA complex-guided pharmacophore modeling approach to screen inhibitors against the response regulator PmrA of polymyxin B-resistant Klebsiella pneumoniae (KP). The identified lead, E1 (IC50 = 10.2 μM), targeted the DNA-binding domain of PmrA (KD = 1.7 μM), whose conserved residues R171, R198, K203, and Y214 have been shown to be hotspots for antimicrobial development. Treatment of E1 restored the susceptibility of KP to polymyxin B.

Graphical abstract: Protein–DNA complex-guided discovery of the antibacterial lead E1 for restoring the susceptibility of Klebsiella Pneumoniae to polymyxin B by targeting the response regulator PmrA

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Publication details

The article was received on 07 Mar 2018, accepted on 21 May 2018 and first published on 24 May 2018


Article type: Communication
DOI: 10.1039/C8CC01840E
Citation: Chem. Commun., 2018,54, 6372-6375
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    Protein–DNA complex-guided discovery of the antibacterial lead E1 for restoring the susceptibility of Klebsiella Pneumoniae to polymyxin B by targeting the response regulator PmrA

    T. Tseng, I. Tu, H. Chen, L. Lin, K. Tsai, S. Wu and C. Chen, Chem. Commun., 2018, 54, 6372
    DOI: 10.1039/C8CC01840E

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