title: Homology model of the DNA gyrase enzyme of Helicobacter pylori, a target of quinolone-based eradication therapy.
abstract: OBJECTIVE
  Resistance of Helicobacter pylori to the standard therapeutic antimicrobial agents has been demonstrated. Although quinolones are an alternative candidate for third-line eradication therapy, quinolone resistance of H. pylori is also increasing. Quinolone resistance of H. pylori is caused by a point mutation of the DNA gyrase subunit A (GyrA) protein, especially on amino acids 87 and 91. The aim of this study is to surmise the structure of H. pylori GryA.
  
  
  METHODS
  The modeling of the 3-D structure of H. pylori GyrA was performed by an automated homology modeling program: SWISS-MODEL. The position of amino acids 87 and 91 in H. pylori GyrA was plotted on the homology model. To estimate the function of quinolone resistance-determining region (QRDR), the structure of H. pylori GyrA was compared with Escherichia coli GyrA.
  
  
  RESULTS
  A molecular model of H. pylori GyrA could be predicted using SWISS-MODEL. The GyrA N- and C-terminal domains closely resembled those of E. coli. The position of amino acids 87 and 91 in H. pylori GyrA was part of the DNA binding region (head dimer interface) on the GyrA N-terminal domain.
  
  
  CONCLUSIONS
  Our homology model of H. pylori GryA suggests that the quinolone resistance-determining region is on the head dimer interface of the GyrA N-terminal domain.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Juntaro
authors.initials: J
authors.lastname: Matsuzaki
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsugawa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nishizawa
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003198:Computer Simulation; D027081:DNA Gyrase / Q000737:chemistry* / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry*; D016480:Helicobacter pylori / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D015363:Quinolones / Q000627:therapeutic use*; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D015363:Quinolones; D027081:DNA Gyrase