1. Identification and characterization of natural microbial products that alter the free d-aspartate content of mammalian cells.
- Author
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Katane M, Kaneko Y, Watanabe M, Doi Y, Tanaka T, Kasuga Y, Yoshida N, Kumakubo S, Nakayama K, Matsuda S, Furuchi T, Saitoh Y, Sekine M, Koyama N, Tomoda H, and Homma H
- Subjects
- Amino Acid Transport System X-AG metabolism, Animals, Aspartic Acid biosynthesis, HEK293 Cells, Humans, PC12 Cells, Plicamycin pharmacology, Rats, Sesquiterpenes pharmacology, Stereoisomerism, Aspartic Acid antagonists & inhibitors, Benzoquinones pharmacology, Lactams, Macrocyclic pharmacology, Plicamycin analogs & derivatives
- Abstract
Mammalian cells possess the molecular apparatus necessary to take up, degrade, synthesize, and release free d-aspartate, which plays an important role in physiological functions within the body. Here, biologically active microbial compounds and pre-existing drugs were screened for their ability to alter the intracellular d-aspartate level in mammalian cells, and several candidate compounds were identified. Detailed analytical studies suggested that two of these compounds, mithramycin A and geldanamycin, suppress the biosynthesis of d-aspartate in cells. Further studies suggested that these compounds act at distinct sites within the cell. These compounds may advance our current understanding of biosynthesis of d-aspartate in mammals, a whole picture of which remains to be disclosed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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