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†,10.1039/C8CC01840E

热搜：

Lactoyl-CoA 全氟丁基戊烷白叶藤碱全氟己基辛烷新白叶藤碱壳寡糖特色专题-生物多肽

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†

Tien-Sheng Tseng,I-Fan Tu,Hsiao-Ting Chen,Lie-Chwen Lin,Shih-Hsiung Wu,Chinpan Chen

Chemical Communications Pub Date : 05/24/2018 00:00:00 , DOI:10.1039/C8CC01840E

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 (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.