1so8
From Proteopedia
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| - | [[Image:1so8.gif|left|200px]] | + | [[Image:1so8.gif|left|200px]] |
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| - | '''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)]''' | + | {{Structure |
| + | |PDB= 1so8 |SIZE=350|CAPTION= <scene name='initialview01'>1so8</scene>, resolution 2.3Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/3-hydroxyacyl-CoA_dehydrogenase 3-hydroxyacyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.35 1.1.1.35] | ||
| + | |GENE= HADH2, ERAB, XH98G2, SCHAD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''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)]''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1SO8 is a [ | + | 1SO8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SO8 OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15087549 15087549] |
[[Category: 3-hydroxyacyl-CoA dehydrogenase]] | [[Category: 3-hydroxyacyl-CoA dehydrogenase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: alcohol dehydrogenase; rossmann fold; abeta-induced distorsion]] | [[Category: alcohol dehydrogenase; rossmann fold; abeta-induced distorsion]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:07:35 2008'' |
Revision as of 12:07, 20 March 2008
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| , resolution 2.3Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | HADH2, ERAB, XH98G2, SCHAD (Homo sapiens) | ||||||
| Activity: | 3-hydroxyacyl-CoA dehydrogenase, with EC number 1.1.1.35 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 |
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. 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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