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Homology model of the DNA gyrase enzyme of Helicobacter pylori , a target of quinolone‐based eradication therapy
Author(s) -
Matsuzaki Juntaro,
Suzuki Hidekazu,
Tsugawa Hitoshi,
Nishizawa Toshihiro,
Hibi Toshifumi
Publication year - 2010
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2010.06245.x
Subject(s) - dna gyrase , quinolone , homology modeling , helicobacter pylori , microbiology and biotechnology , homology (biology) , amino acid , escherichia coli , medicine , biology , genetics , biochemistry , enzyme , antibiotics , gene
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.