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NMR structural characterization of the N‐terminal active domain of the gyrase B subunit from Pseudomonas aeruginosa and its complex with an inhibitor
Author(s) -
Li Yan,
Wong Yun Xuan,
Poh Zhi Ying,
Wong Ying Lei,
Lee Michelle Yueqi,
Ng Hui Qi,
Liu Boping,
Hung Alvin W.,
Cherian Joseph,
Hill Jeffrey,
Keller Thomas H.,
Kang CongBao
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.07.044
Subject(s) - dna gyrase , pseudomonas aeruginosa , chemistry , protein subunit , drug discovery , nuclear magnetic resonance spectroscopy , docking (animal) , biophysics , biochemistry , stereochemistry , escherichia coli , biology , bacteria , genetics , nursing , gene , medicine
The N‐terminal ATP binding domain of the DNA gyrase B subunit is a validated drug target for antibacterial drug discovery. Structural information for this domain (pGyrB) from Pseudomonas aeruginosa is still missing. In this study, the interaction between pGyrB and a bis ‐pyridylurea inhibitor was characterized using several biophysical methods. We further carried out structural analysis of pGyrB using NMR spectroscopy. The secondary structures of free and inhibitor bound pGyrB were obtained based on backbone chemical shift assignment. Chemical shift perturbation and NOE experiments demonstrated that the inhibitor binds to the ATP binding pocket. The results of this study will be helpful for drug development targeting P. aeruginosa .