1so8

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Revision as of 17:09, 12 November 2007

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spinqualitylabelsall models 1so8, resolution 2.3Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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)]

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency OMIM:[300256], 3-hydroxyacyl-CoA dehydrogenase deficiency OMIM:[601609], Hyperinsulinemic hypoglycemia, familial, 4 OMIM:[601609]

About this Structure

1SO8 is a Single protein structure of sequence from Homo sapiens with NA and CL as ligands. Active as 3-hydroxyacyl-CoA dehydrogenase, with EC number 1.1.1.35 Full crystallographic information is available from OCA.

Reference

ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease., Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H, Science. 2004 Apr 16;304(5669):448-52. PMID:15087549

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