caa a22 4500 463185447 CHVBK 20180406164851.0 cr unu---uuuuu 170326e20070101xx s 000 0 eng 10.1007/s00726-006-0348-4 doi (NATIONALLICENCE)springer-10.1007/s00726-006-0348-4 Isolation and characterization of mammalian D -aspartyl endopeptidase [Elektronische Daten] [T. Kinouchi, H. Nishio, Y. Nishiuchi, M. Tsunemi, K. Takada, T. Hamamoto, Y. Kagawa, N. Fujii] Summary.: 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]-CH2Cl; MW: 563.01), was newly synthesized and inhibited DAEP activity (IC50, 3 µM), 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. Springer-Verlag, 2006 Keywords: D -Aspartate - Protease - Mitochondria - Alzheimer's disease - Amyloid nationallicence Kinouchi T. Department of Radiation Life Science and Radiation Medical Science, Research Reactor Institute, Kyoto University, Osaka, Japan aut Nishio H. Peptide Institute, Inc., Osaka, Japan aut Nishiuchi Y. Peptide Institute, Inc., Osaka, Japan aut Tsunemi M. Peptide Institute, Inc., Osaka, Japan aut Takada K. Peptide Institute, Inc., Osaka, Japan aut Hamamoto T. Department of Biochemistry, Jichi Medical School, Tochigi, Japan aut Kagawa Y. Department of Medical Chemistry, Women's University of Nutrition, Saitama, Japan aut Fujii N. Department of Radiation Life Science and Radiation Medical Science, Research Reactor Institute, Kyoto University, Osaka, Japan aut Amino Acids Springer-Verlag 32/1(2007-01-01), 79-85 0939-4451 32:1<79 2007 32 726 https://doi.org/10.1007/s00726-006-0348-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00726-006-0348-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kinouchi T. Department of Radiation Life Science and Radiation Medical Science, Research Reactor Institute, Kyoto University, Osaka, Japan aut NATIONALLICENCE 700 1- Nishio H. Peptide Institute, Inc., Osaka, Japan aut NATIONALLICENCE 700 1- Nishiuchi Y. Peptide Institute, Inc., Osaka, Japan aut NATIONALLICENCE 700 1- Tsunemi M. Peptide Institute, Inc., Osaka, Japan aut NATIONALLICENCE 700 1- Takada K. Peptide Institute, Inc., Osaka, Japan aut NATIONALLICENCE 700 1- Hamamoto T. Department of Biochemistry, Jichi Medical School, Tochigi, Japan aut NATIONALLICENCE 700 1- Kagawa Y. Department of Medical Chemistry, Women's University of Nutrition, Saitama, Japan aut NATIONALLICENCE 700 1- Fujii N. Department of Radiation Life Science and Radiation Medical Science, Research Reactor Institute, Kyoto University, Osaka, Japan aut NATIONALLICENCE 773 0- Amino Acids Springer-Verlag 32/1(2007-01-01), 79-85 0939-4451 32:1<79 2007 32 726 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer