1so8: Difference between revisions
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New page: left|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'' | ||
