2011年11月
Substrate stereoselectivity of mammalian D-aspartyl endopeptidase
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
- ,
- ,
- 巻
- 879
- 号
- 29
- 開始ページ
- 3349
- 終了ページ
- 3352
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.jchromb.2011.08.031
- 出版者・発行元
- ELSEVIER SCIENCE BV
The formation and accumulation of D-aspartate residue (D-Asp) in proteins caused by oxidative stress leads to dysfunction and/or denaturation of proteins, and is consequently responsible for aging-related misfolding diseases such as cataracts, prion disease, and Alzheimer's disease. We sought to identify that an unknown protease selectively degrades the noxious D-Asp-containing protein, namely D-aspartyl endopeptidase (DAEP), and finally purified it from the inner mitochondrial membrane of mouse liver. In order to analyze the substrate stereoselectivity of DAEP, we synthesized a peptide corresponding to 55-65 (Thr-Val-Leu-Asp-Ser-Gly-Ile-Ser-Glu-Val-Arg) of human alpha A-crystallin and its corresponding diastereoisomers in which L-alpha-Asp was replaced with L-beta-, D-alpha- or D-beta-Asp residue at position 58. Following incubation of that peptide with purified DAEP, it was only degraded at D-alpha-Asp(58), independent of ATP or NAD. This result indicates that DAEP stereoselectively recognizes and degrades its substrate at the internal D-alpha-Asp residue. DAEP therefore seems to physiologically serve as the quality control system against the noxious D-Asp-containing protein in the long life span of mammals. (C) 2011 Published by Elsevier B.V.
- リンク情報
- ID情報
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- DOI : 10.1016/j.jchromb.2011.08.031
- ISSN : 1570-0232
- PubMed ID : 21944696
- Web of Science ID : WOS:000297141500036