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)]


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.231 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease.

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.

(2004) Science 304: 448-452

  • DOI: https://doi.org/10.1126/science.1091230
  • Primary Citation of Related Structures:  
    1SO8

  • 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.


  • Organizational Affiliation

    Center for Reproductive Sciences and Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-hydroxyacyl-CoA dehydrogenase type II261Homo sapiensMutation(s): 0 
Gene Names: HADH2ERABXH98G2SCHAD
EC: 1.1.1.35 (PDB Primary Data), 1.1.1.53 (UniProt), 1.1.1.62 (UniProt), 1.1.1.178 (UniProt), 1.1.1.239 (UniProt), 1.1.1.159 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for Q99714 (Homo sapiens)
Explore Q99714 
Go to UniProtKB:  Q99714
PHAROS:  Q99714
GTEx:  ENSG00000072506 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99714
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.231 
  • Space Group: P 4 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 130α = 90
b = 130β = 90
c = 130γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
GLRFphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-05-11
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations