1SO8

Abeta-bound human ABAD structure [also known as 3-hydroxyacyl-CoA dehydrogenase type II (Type II HADH), Endoplasmic reticulum-associated amyloid beta-peptide binding protein (ERAB)]

Summary for 1SO8

• Entry DOI: 10.2210/pdb1so8/pdb
• Descriptor: 3-hydroxyacyl-CoA dehydrogenase type II, SODIUM ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: alcohol dehydrogenase; rossmann fold; abeta-induced distorsion, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion: Q99714
• Total number of polymer chains: 1
• Total formula weight: 27028.45

Authors

Lustbader, J.W.,Cirilli, M.,Wu, H. (deposition date: 2004-03-13, release date: 2004-05-11, Last modification date: 2024-02-14)

Primary citation

Lustbader, J.W.,Cirilli, M.,Lin, C.,Xu, H.W.,Takuma, K.,Wang, N.,Caspersen, C.,Chen, X.,Pollak, S.,Chaney, M.,Trinchese, F.,Gunn-Moore, F.,Lue, L.F.,Walker, D.G.,Kuppusamy, P.,Zewier, Z.L.,Arancio, O.,Stern, D.,Yan, S.S.,Wu, H.
ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease.
Science, 304:448-452, 2004

PubMed Abstract: Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal toxicity in Alzheimer's disease (AD). Here, we demonstrate that Abeta-binding alcohol dehydrogenase (ABAD) is a direct molecular link from Abeta to mitochondrial toxicity. Abeta interacts with ABAD in the mitochondria of AD patients and transgenic mice. The crystal structure of Abeta-bound ABAD shows substantial deformation of the active site that prevents nicotinamide adenine dinucleotide (NAD) binding. An ABAD peptide specifically inhibits ABAD-Abeta interaction and suppresses Abeta-induced apoptosis and free-radical generation in neurons. Transgenic mice overexpressing ABAD in an Abeta-rich environment manifest exaggerated neuronal oxidative stress and impaired memory. These data suggest that the ABAD-Abeta interaction may be a therapeutic target in AD.

PubMed: 15087549
DOI: 10.1126/science.1091230

Experimental method

X-RAY DIFFRACTION (2.3 Å)