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Structural and enzymatic properties of mammalian d-glutamate cyclase
- Katane, Masumi, Ariyoshi, Makoto, Tateishi, Shuhei, Koiwai, Sachi, Takaku, Kaoruko, Nagai, Kenichiro, Nakayama, Kazuki, Saitoh, Yasuaki, Miyamoto, Tetsuya, Sekine, Masae, Mita, Masashi, Hamase, Kenji, Matoba, Satoaki, Homma, Hiroshi
- Archives of biochemistry and biophysics 2018 v.654 pp. 10-18
- adenosine diphosphate, adenosine triphosphate, cardiac output, catalytic activity, cations, enzyme activity, glutamic acid, heart, heart failure, manganese, mice, mitochondria, oligomerization, pH, risk
- 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.