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Transferred NOE and Saturation Transfer Difference NMR Studies of Novobiocin Binding to EnvZ Suggest Binding Mode Similar to DNA Gyrase
Author(s) -
Plesniak Leigh A.,
Botsch Kyle,
Leibrand Michelle,
Kelly Mark,
Sem Daniel,
Adams Joseph A.,
Jennings Patricia
Publication year - 2008
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2007.00607.x
Subject(s) - novobiocin , dna gyrase , histidine kinase , biochemistry , biology , histidine , dna , binding site , biophysics , escherichia coli , enzyme , gene , antibiotics
Histidine protein kinases (HPKs) are a class of receptor proteins found in bacterial two‐component signal transduction systems, which allow bacteria to respond to changes in their external environment. To date, there are few potent inhibitors of histidine kinases, despite their potential ability to weaken bacteria against antibiotic treatment. EnvZ is a histidine protein kinase with osmoregulatory function in bacteria with sequence and topological similarity to DNA Gyrase B. DNA Gyrase B has several well‐characterized potent inhibitors, including novobiocin and clorobiocin which have detailed structures in complex. With fluorescence competition experiments, we have determined that novobiocin binds to EnvZ with a novo K D 120 ± 20 μ m . NMR transferred NOE (trNOE) experiments, and saturation transfer difference (STD) experiments suggest that novobiocin binds to EnvZ in a conformation and orientation similar to its binding with DNA Gyrase B. These experiments suggest some similarity in the pocket despite weaker affinity for EnvZ by novobiocin.