NMR structural characterization of the N-terminal active domain of the gyrase B subunit from Pseudomonas aeruginosa and its complex with an inhibitor.
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.
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Yan
Y
Li
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Yun Xuan
YX
Wong
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Zhi Ying
ZY
Poh
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Ying Lei
YL
Wong
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Michelle Yueqi
MY
Lee
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Hui Qi
HQ
Ng
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Boping
B
Liu
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Alvin W
AW
Hung
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Joseph
J
Cherian
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Jeffrey
J
Hill
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore.
Thomas H
TH
Keller
Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669, Singapore. Electronic address: cbkang@etc.a-star.edu.sg.
CongBao
C
Kang
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D027081:DNA Gyrase / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014508:Urea / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D059005:Topoisomerase II Inhibitors; D000255:Adenosine Triphosphate; D014508:Urea; D027081:DNA Gyrase
Drug discovery; Gyrase B; NMR; Structure-based drug design; Topoisomerase