Protein-DNA complex-guided discovery of the antibacterial lead for restoring the susceptibility of to polymyxin B by targeting the response regulator PmrA
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 (IC 50 = 10.2 μM), targeted the DNA-binding doma...
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| Published in | Chemical communications (Cambridge, England) Vol. 54; no. 49; pp. 6372 - 6375 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Published |
14.06.2018
|
| Online Access | Get full text |
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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
(IC
50
= 10.2 μM), targeted the DNA-binding domain of PmrA (
K
D
= 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.
E1
, a novel adjuvant lead, restored the susceptibility of
Klebsiella Pneumoniae
to Polymyxin B by targeting the response regulator PmrA. |
|---|---|
| AbstractList | 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
(IC
50
= 10.2 μM), targeted the DNA-binding domain of PmrA (
K
D
= 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.
E1
, a novel adjuvant lead, restored the susceptibility of
Klebsiella Pneumoniae
to Polymyxin B by targeting the response regulator PmrA. |
| Author | Tsai, Keng-Chang Chen, Hsiao-Ting Lin, Lie-Chwen Wu, Shih-Hsiung Chen, Chinpan Tseng, Tien-Sheng Tu, I-Fan |
| AuthorAffiliation | Institute of Biomedical Sciences The PhD Program for Medical Biotechnology National Research Institute of Chinese Medicine Academia Sinica College of Medical Science and Technology Institute of Biological Chemistry Ministry of Health and Welfare Taipei Medical University |
| AuthorAffiliation_xml | – name: Institute of Biological Chemistry – name: Ministry of Health and Welfare – name: Academia Sinica – name: National Research Institute of Chinese Medicine – name: Taipei Medical University – name: College of Medical Science and Technology – name: The PhD Program for Medical Biotechnology – name: Institute of Biomedical Sciences |
| Author_xml | – sequence: 1 givenname: Tien-Sheng surname: Tseng fullname: Tseng, Tien-Sheng – sequence: 2 givenname: I-Fan surname: Tu fullname: Tu, I-Fan – sequence: 3 givenname: Hsiao-Ting surname: Chen fullname: Chen, Hsiao-Ting – sequence: 4 givenname: Lie-Chwen surname: Lin fullname: Lin, Lie-Chwen – sequence: 5 givenname: Keng-Chang surname: Tsai fullname: Tsai, Keng-Chang – sequence: 6 givenname: Shih-Hsiung surname: Wu fullname: Wu, Shih-Hsiung – sequence: 7 givenname: Chinpan surname: Chen fullname: Chen, Chinpan |
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| Title | Protein-DNA complex-guided discovery of the antibacterial lead for restoring the susceptibility of to polymyxin B by targeting the response regulator PmrA |
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