title: Mammalian D-aspartyl endopeptidase: a scavenger for noxious racemized proteins in aging.
abstract: The accumulation of D-isomers of aspartic acid (D-Asp) in proteins during aging has been implicated in the pathogenesis of Alzheimer's disease, 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: 600kDa) and is localized in the inner mitochondrial membrane of mouse and rabbit, but DAEP activity was not detected in Escherichia coli, Saccharomyces cerevisiae, and Caenorhabditis elegans. A specific inhibitor for DAEP was newly synthesized, and inhibited DAEP activity (IC(50), 3microM), a factor of 10 greater than lactacystin on DAEP. On the other hand, the inhibitor did not inhibit either the 20S or 26S proteasome.
authors.affiliation: Department of Biochemistry, Jichi Medical School, 329-0498, Tochigi, Japan. kinouchi@jichi.ac.jp
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Kinouchi
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ishiura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mabuchi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Urakami-Manaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishio
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishiuchi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsunemi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Takada
authors.forename: Masatomo
authors.initials: M
authors.lastname: Watanabe
authors.forename: Masashi
authors.initials: M
authors.lastname: Ikeda
authors.forename: Hisao
authors.initials: H
authors.lastname: Matsui
authors.forename: Shigeo
authors.initials: S
authors.lastname: Tomioka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawahara
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hamamoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kagawa
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005260:Female; D007536:Isomerism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008930:Mitochondria, Liver / Q000201:enzymology; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D009842:Oligopeptides; D011480:Protease Inhibitors; D001224:Aspartic Acid; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D016282:Aspartic Acid Endopeptidases