Structural and enzymatic properties of mammalian d-glutamate cyclase
| Autor: | Masumi Katane, Sachi Koiwai, Makoto Ariyoshi, Yasuaki Saitoh, Kazuki Nakayama, Satoaki Matoba, Kenji Hamase, Hiroshi Homma, Shuhei Tateishi, Tetsuya Miyamoto, Kenichiro Nagai, Masashi Mita, Kaoruko Takaku, Masae Sekine |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proline Protein Conformation Biophysics Glutamic Acid Mitochondrion Biochemistry Cyclase Catalysis Substrate Specificity Divalent Mice 03 medical and health sciences 0302 clinical medicine Animals Nucleotide Molecular Biology Hydro-Lyases chemistry.chemical_classification Manganese biology Glutamic acid Hydrogen-Ion Concentration Recombinant Proteins Enzyme assay Mitochondria Kinetics 030104 developmental biology Enzyme chemistry Mitochondrial matrix biology.protein Electrophoresis Polyacrylamide Gel Dimerization 030217 neurology & neurosurgery |
| Zdroj: | Archives of Biochemistry and Biophysics. 654:10-18 |
| ISSN: | 0003-9861 |
| DOI: | 10.1016/j.abb.2018.07.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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