Inactivation of NikR from Helicobacter pylori by a bismuth drug

J Inorg Biochem. 2019 Jul:196:110685. doi: 10.1016/j.jinorgbio.2019.03.025. Epub 2019 Apr 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Bismuth / chemistry*
  • Bismuth / pharmacology*
  • Gene Expression Regulation, Bacterial / drug effects
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / metabolism*
  • Nickel / chemistry
  • Protein Binding
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*

Substances

  • Bacterial Proteins
  • NikR protein, Helicobacter pylori
  • Repressor Proteins
  • Nickel
  • Bismuth