1so8
From Proteopedia
(New page: 200px<br /> <applet load="1so8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1so8, resolution 2.3Å" /> '''Abeta-bound human AB...) |
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| - | [[Image:1so8.gif|left|200px]]<br /> | + | [[Image:1so8.gif|left|200px]]<br /><applet load="1so8" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1so8" size=" | + | |
caption="1so8, resolution 2.3Å" /> | caption="1so8, resolution 2.3Å" /> | ||
'''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)]'''<br /> | '''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)]'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1SO8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NA and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1SO8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SO8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Cirilli, M.]] | [[Category: Cirilli, M.]] | ||
| - | [[Category: Lustbader, J | + | [[Category: Lustbader, J W.]] |
[[Category: Wu, H.]] | [[Category: Wu, H.]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: alcohol dehydrogenase; rossmann fold; abeta-induced distorsion]] | [[Category: alcohol dehydrogenase; rossmann fold; abeta-induced distorsion]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:03:30 2008'' |
Revision as of 13:03, 21 February 2008
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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)]
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 with and 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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