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Binding of amyloid β‐peptide to mitochondrial hydroxyacyl‐CoA dehydrogenase (ERAB): regulation of an SDR enzyme activity with implications for apoptosis in Alzheimer's disease
Author(s) -
Oppermann Udo C.T.,
Salim Samina,
Tjernberg Lars O.,
Terenius Lars,
Jörnvall Hans
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00586-4
Subject(s) - enzyme , alzheimer's disease , apoptosis , biochemistry , mitochondrion , peptide , chemistry , dehydrogenase , disease , medicine
The intracellular amyloid β‐peptide (Aβ) binding protein, ERAB, a member of the short‐chain dehydrogenase/reductase (SDR) family, is known to mediate apoptosis in different cell lines and to be a class II hydroxyacyl‐CoA dehydrogenase. The Aβ peptide inhibits the enzymatic reaction in a mixed type fashion with a K i of 1.2 μmol/l and a K i ES of 0.3 μmol/l, using 3‐hydroxybutyryl‐CoA. The peptide region necessary for inhibition comprises residues 12–24 of Aβ1–40, covering the 16–20 fragment, which is the minimum sequence for the blockade of Aβ polymerization, but that minimal fragment is not sufficient for more than marginal inhibition. The localization of ERAB to the endoplasmic reticulum and mitochondria suggests a complex interaction with components of the programmed cell death machinery. The interaction of Aβ with ERAB further links oxidoreductase activity with both apoptosis and amyloid toxicity.