Structural and enzymatic properties of mammalian D-glutamate cyclase

Masumi Katane, Makoto Ariyoshi, Shuhei Tateishi, Sachi Koiwai, Kaoruko Takaku, Kenichiro Nagai, Kazuki Nakayama, Yasuaki Saitoh, Tetsuya Miyamoto, Masae Sekine, Masashi Mita, Kenji Hamase, Satoaki Matoba, Hiroshi Homma

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

D-Glutamate cyclase (DGLUCY) is a unique enzyme that reversibly converts free D-glutamate to 5-oxo-D-proline and H2O. Mammalian DGLUCY is highly expressed in the mitochondrial matrix in the heart, and its downregulation disrupts D-glutamate and/or 5-oxo-D-proline levels, contributing to the onset and/or exacerbation of heart failure. However, detailed characterisation of DGLUCY has not yet been performed. Herein, the structural and enzymatic properties of purified recombinant mouse DGLUCY were examined. The results revealed a dimeric oligomerisation state, and both D-glutamate-to-5-oxo-D-proline and 5-oxo-D-proline-to-D-glutamate reactions were catalysed in a stereospecific manner. Catalytic activity is modulated by divalent cations and nucleotides including ATP and ADP. Interestingly, the presence of Mn2+ completely abolished the 5-oxo-D-proline-to-D-glutamate reaction but stimulated the D-glutamate-to-5-oxo-D-proline reaction. The optimum pH is ∼8.0, similar to that in the mitochondrial matrix, and the catalytic efficiency for D-glutamate is markedly higher than that for 5-oxo-D-proline. These findings suggest that DGLUCY functions as a metalloenzyme that degrades D-glutamate in the mitochondrial matrix in mammalian cells. The results also provide insight into the correlation between DGLUCY enzyme activity and the physiological and pathological roles of D-glutamate and 5-oxo-D-proline in cardiac function, which is of relevance to the risk of onset of heart failure.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume654
DOIs
Publication statusPublished - Sep 15 2018

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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