Crystal structure of a Bombyx mori sigma-class glutathione transferase exhibiting prostaglandin e synthase activity

Kohji Yamamoto, Akifumi Higashiura, Mamoru Suzuki, Kosuke Aritake, Yoshihiro Urade, Nobuko Uodome, Atsushi Nakagawa

Research output: Contribution to journalArticle

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Abstract

Background Glutathione transferases (GSTs) are members of a major family of detoxification enzymes. Here, we report the crystal structure of a sigma-class GST of Bombyx mori, bmGSTS1, to gain insight into the mechanism catalysis. Methods The structure of bmGSTS1 and its complex with glutathione were determined at resolutions of 1.9 Å and 1.7 Å by synchrotron radiation and the molecular replacement method. Results The three-dimensional structure of bmGSTS1 shows that it exists as a dimer and is similar in structure to other GSTs with respect to its secondary and tertiary structures. Although striking similarities to the structure of prostaglandin D synthase were also detected, we were surprised to find that bmGSTS1 can convert prostaglandin H2 into its E2 form. Comparison of bmGSTS1 with its glutathione complex showed that bound glutathione was localized to the glutathione-binding site (G-site). Site-directed mutagenesis of bmGSTS1 mutants indicated that amino acid residues Tyr8, Leu14, Trp39, Lys43, Gln50, Met51, Gln63, and Ser64 in the G-site contribute to catalytic activity. Conclusion We determined the tertiary structure of bmGSTS1 exhibiting prostaglandin E synthase activity. General significance These results are, to our knowledge, the first report of a prostaglandin synthase activity in insects.

Original languageEnglish
Pages (from-to)3711-3718
Number of pages8
JournalBiochimica et Biophysica Acta - General Subjects
Volume1830
Issue number6
DOIs
Publication statusPublished - Jun 1 2013

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Bombyx
Prostaglandin-Endoperoxide Synthases
Glutathione Transferase
Prostaglandins
Glutathione
Crystal structure
prostaglandin R2 D-isomerase
Binding Sites
Prostaglandin H2
Detoxification
Mutagenesis
Synchrotrons
Site-Directed Mutagenesis
Prostaglandins E
Synchrotron radiation
Catalysis
Dimers
Insects
Catalyst activity
Radiation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Crystal structure of a Bombyx mori sigma-class glutathione transferase exhibiting prostaglandin e synthase activity. / Yamamoto, Kohji; Higashiura, Akifumi; Suzuki, Mamoru; Aritake, Kosuke; Urade, Yoshihiro; Uodome, Nobuko; Nakagawa, Atsushi.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1830, No. 6, 01.06.2013, p. 3711-3718.

Research output: Contribution to journalArticle

Yamamoto, Kohji ; Higashiura, Akifumi ; Suzuki, Mamoru ; Aritake, Kosuke ; Urade, Yoshihiro ; Uodome, Nobuko ; Nakagawa, Atsushi. / Crystal structure of a Bombyx mori sigma-class glutathione transferase exhibiting prostaglandin e synthase activity. In: Biochimica et Biophysica Acta - General Subjects. 2013 ; Vol. 1830, No. 6. pp. 3711-3718.
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AB - Background Glutathione transferases (GSTs) are members of a major family of detoxification enzymes. Here, we report the crystal structure of a sigma-class GST of Bombyx mori, bmGSTS1, to gain insight into the mechanism catalysis. Methods The structure of bmGSTS1 and its complex with glutathione were determined at resolutions of 1.9 Å and 1.7 Å by synchrotron radiation and the molecular replacement method. Results The three-dimensional structure of bmGSTS1 shows that it exists as a dimer and is similar in structure to other GSTs with respect to its secondary and tertiary structures. Although striking similarities to the structure of prostaglandin D synthase were also detected, we were surprised to find that bmGSTS1 can convert prostaglandin H2 into its E2 form. Comparison of bmGSTS1 with its glutathione complex showed that bound glutathione was localized to the glutathione-binding site (G-site). Site-directed mutagenesis of bmGSTS1 mutants indicated that amino acid residues Tyr8, Leu14, Trp39, Lys43, Gln50, Met51, Gln63, and Ser64 in the G-site contribute to catalytic activity. Conclusion We determined the tertiary structure of bmGSTS1 exhibiting prostaglandin E synthase activity. General significance These results are, to our knowledge, the first report of a prostaglandin synthase activity in insects.

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