Homology model of the DNA gyrase enzyme of Helicobacter pylori, a target of quinolone-based eradication therapy

Juntaro Matsuzaki, Hidekazu Suzuki, Hitoshi Tsugawa, Toshihiro Nishizawa, Toshifumi Hibi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background and Aims: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)S7-S10
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume25
Issue numberSUPPL. 1
DOIs
Publication statusPublished - 2010 May

Keywords

  • DNA gyrase
  • Helicobacter pylori
  • Quinolones

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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