The NikR protein is an essential DNA regulator of Helicobacter pylori, a human pathogen, which infects almost half of the world's population. Herein, we comprehensively characterized the interaction of a bismuth drug with Helicobacter pylori NikR. We show that Bi(III) can occupy the high-affinity Ni(II) site of NikR. The highly-conserved residue Cys107 at this site is critical for Bi(III) binding. Importantly, such a binding disassembles physiologically functional NikR tetramer into inactive dimer, leading to abrogation of the DNA-binding capability of NikR. Bi(III)-binding also significantly disturbs regulatory function of Helicobacter pylori NikR in vivo. Therefore, NikR might serve as a potential intracellular target of a bismuth drug.
Keywords: Bismuth drug; DNA regulator; Helicobacter pylori; Metal-binding.
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