title: Solution NMR studies on Helicobacter pylori proteins for antibiotic target discovery.
abstract: BACKGROUND
  Helicobacter pylori (H. pylori) is a well-known widespread pathogenic bacterium that survives in the extremely acidic conditions of the human gastric mucosa. The global prevalence of H. pylori-resistant antibiotics has become an emerging issue in the 21st century and has necessitated the development of novel antibiotic drugs. Many efforts have aimed to discover antibiotic target proteins of H. pylori based on its genome of more than 1600 genes.
  
  
  METHODS
  This article highlights NMR spectroscopy as a valuable tool for determining the structure and dynamics of potential antibiotic-targeted proteins of H. pylori and evaluating their modes of interaction with native or synthetic binding partners. The residue-specific information on binding in solution provides a structural basis to identify and optimize lead compounds.
  
  
  CONCLUSIONS
  NMR spectroscopy is a powerful method for obtaining details of biomolecular interactions with a broad range of binding affinities. This strength facilitates the identification of the binding interface of the encounter complex that plays an integral role in a variety of biological functions. This low-affinity complex is difficult to crystallize, which impedes structure determination using X-ray crystallography. Additionally, the relative binding affinities can be predicted from the type of spectral change upon binding. High-resolution NMR spectroscopy in combination with advanced computer simulation would provide more confidence in complex structures. The application of NMR to studies of the H. pylori protein could contribute to the development of these targeted novel antibiotics.
authors.affiliation: a Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul , Korea.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Lee
authors.affiliation: a Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul , Korea.
authors.forename: Bong-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D058990:Molecular Targeted Therapy
chemical_list: D000900:Anti-Bacterial Agents
keywords: Helicobacter pylori proteins; NMR spectroscopy; antibiotic target; biomolecular interaction; dynamics; tertiary structure