1so8
From Proteopedia
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|PDB= 1so8 |SIZE=350|CAPTION= <scene name='initialview01'>1so8</scene>, resolution 2.3Å | |PDB= 1so8 |SIZE=350|CAPTION= <scene name='initialview01'>1so8</scene>, resolution 2.3Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= HADH2, ERAB, XH98G2, SCHAD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= HADH2, ERAB, XH98G2, SCHAD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1so8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1so8 OCA], [http://www.ebi.ac.uk/pdbsum/1so8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1so8 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300256 300256]], 3-hydroxyacyl-CoA dehydrogenase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601609 601609]], Hyperinsulinemic hypoglycemia, familial, 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601609 601609]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Lustbader, J W.]] | [[Category: Lustbader, J W.]] | ||
[[Category: Wu, H.]] | [[Category: Wu, H.]] | ||
| - | [[Category: | + | [[Category: abeta-induced distorsion]] |
| - | [[Category: | + | [[Category: alcohol dehydrogenase]] |
| - | [[Category: | + | [[Category: rossmann fold]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:44:47 2008'' |
Revision as of 20:44, 30 March 2008
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| , resolution 2.3Å | |||||||
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| Ligands: | , | ||||||
| Gene: | HADH2, ERAB, XH98G2, SCHAD (Homo sapiens) | ||||||
| Activity: | 3-hydroxyacyl-CoA dehydrogenase, with EC number 1.1.1.35 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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)]
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.
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
Page seeded by OCA on Sun Mar 30 23:44:47 2008
