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Isolation and characterization of mammalian D-aspartyl endopeptidase.

Isolation and characterization of mammalian D-aspartyl endopeptidase. Research Abstract Details 

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  • Isolation and characterization of mammalian D-aspartyl endopeptidase. Abstract Text:

    t kinouchiT Kinouchi,h nishioH Nishio,y nishiuchiY Nishiuchi,m tsunemiM Tsunemi,k takadaK Takada,t hamamotoT Hamamoto,y kagawaY Kagawa,n fujiiN Fujii,

    The accumulation of D-isomers of aspartic acid (D-Asp) in proteins during aging has been implicated in the pathogenesis of Alzheimer's disease (AD), cataracts and arteriosclerosis. Here, we identified a specific lactacystin-sensitive endopeptidase that cleaves the D-Asp-containing protein and named it D-aspartyl endopeptidase (DAEP). DAEP has a multi-complex structure (MW: 600 kDa) and is localized in the inner mitochondrial membrane. However, DAEP activity was not detected in E. coli, S. cerevisiae, and C. elegans. A specific inhibitor for DAEP, i-DAEP: (benzoyl-L-Arg-L-His-[D-Asp]-CH(2)Cl; MW: 563.01), was newly synthesized and inhibited DAEP activity (IC(50), 3 microM), a factor of ten greater than lactacystin on DAEP. On the other hand, i-DAEP did not inhibit either the 20S or 26S proteasome. And we identified succinate dehydrogenase and glutamate dehydrogenase 1 as components of DAEP by affinity label using biotinylated i-DAEP. In the long life span of mammals, DAEP may serve as a scavenger against accumulation of racemized proteins in aging. Insights into DAEP will provide the foundation for developing treatments of diseases, such as AD, in which accumulation of D-Asp-containing proteins are implicated.

    Isolation and characterization of mammalian D-aspartyl endopeptidase. Publishing Authors By Initials

    t kinouchiT Kinouchi,h nishioH Nishio,y nishiuchiY Nishiuchi,m tsunemiM Tsunemi,k takadaK Takada,t hamamotoT Hamamoto,y kagawaY Kagawa,n fujiiN Fujii,

    For similar macromolecular substances: multiprotein complexes: multienzyme complexes: succinate cytochrome c oxidoreductase: electron transport complex ii: succinate dehydrogenase research abstracts see: macromolecular substances: multiprotein complexes: multienzyme complexes: succinate cytochrome c oxidoreductase: electron transport complex ii: succinate dehydrogenase research

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    Isolation and characterization of mammalian D-aspartyl endopeptidase. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Amino acids

    VOLUME: 32

    Page Numbers: 79-85

    Journal Abbreviation: Amino Acids

    ISSN: 0939-4451

    DAY: 6

    MONTH: 10

    YEAR: 2006

    Isolation and characterization of mammalian D-aspartyl endopeptidase. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 9200312

    Isolation and characterization of mammalian D-aspartyl endopeptidase. Keywords Mesh Terms:

    KEYWORDS: Succinate Dehydrogenase

    MESH TERMS: isolation & purification

    Chemical & Substance for Abstract: Isolation and characterization of mammalian D-aspartyl endopeptidase. Information

    Substance Name: Proteasome Endopeptidase Complex

    Registry Number: EC 3.4.25.1

    Grant and Affiliation Information for Isolation and characterization of mammalian D-aspartyl endopeptidase.

    AFFILIATION: Department of Radiation Life Science and Radiation Medical Science, Research Reactor Institute, Kyoto University, Osaka, Japan. kinouchi@HL.rri.kyoto-u.ac.jp

    Country: Austria

    Austria Research PublicationAustria Research Publication

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    MEDLINETA: Amino Acids

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