1zum
From Proteopedia
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| - | [[Image:1zum.gif|left|200px]] | + | [[Image:1zum.gif|left|200px]] |
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| - | '''Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, Apo Form''' | + | {{Structure |
| + | |PDB= 1zum |SIZE=350|CAPTION= <scene name='initialview01'>1zum</scene>, resolution 2.10Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=GAI:GUANIDINE'>GAI</scene> and <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Aldehyde_dehydrogenase_(NAD(+)) Aldehyde dehydrogenase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.3 1.2.1.3] | ||
| + | |GENE= ALDH2, ALDM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, Apo Form''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ZUM is a [ | + | 1ZUM 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=1ZUM OCA]. |
==Reference== | ==Reference== | ||
| - | Disruption of the coenzyme binding site and dimer interface revealed in the crystal structure of mitochondrial aldehyde dehydrogenase "Asian" variant., Larson HN, Weiner H, Hurley TD, J Biol Chem. 2005 Aug 26;280(34):30550-6. Epub 2005 Jun 27. PMID:[http:// | + | Disruption of the coenzyme binding site and dimer interface revealed in the crystal structure of mitochondrial aldehyde dehydrogenase "Asian" variant., Larson HN, Weiner H, Hurley TD, J Biol Chem. 2005 Aug 26;280(34):30550-6. Epub 2005 Jun 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15983043 15983043] |
[[Category: Aldehyde dehydrogenase (NAD(+))]] | [[Category: Aldehyde dehydrogenase (NAD(+))]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: rossman fold]] | [[Category: rossman fold]] | ||
| - | ''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 15:40:05 2008'' |
Revision as of 13:40, 20 March 2008
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| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | ALDH2, ALDM (Homo sapiens) | ||||||
| Activity: | Aldehyde dehydrogenase (NAD(+)), with EC number 1.2.1.3 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, Apo Form
Contents |
Overview
Mitochondrial aldehyde dehydrogenase (ALDH2) is the major enzyme that oxidizes ethanol-derived acetaldehyde. A nearly inactive form of the enzyme, ALDH2*2, is found in about 40% of the East Asian population. This variant enzyme is defined by a glutamate to lysine substitution at residue 487 located within the oligomerization domain. ALDH2*2 has an increased Km for its coenzyme, NAD+, and a decreased kcat, which lead to low activity in vivo. Here we report the 2.1 A crystal structure of ALDH2*2. The structure shows a large disordered region located at the dimer interface that includes much of the coenzyme binding cleft and a loop of residues that form the base of the active site. As a consequence of these structural changes, the variant enzyme exhibits rigid body rotations of its catalytic and coenzyme-binding domains relative to the oligomerization domain. These structural perturbations are the direct result of the inability of lysine 487 to form important stabilizing hydrogen bonds with arginines 264 and 475. Thus, the elevated Km for coenzyme exhibited by this variant probably reflects the energetic penalty for reestablishing this site for productive coenzyme binding, whereas the structural alterations near the active site are consistent with the lowered Vmax.
Disease
Known diseases associated with this structure: Alcohol intolerance, acute OMIM:[100650], Fetal alcohol syndrome OMIM:[100650]
About this Structure
1ZUM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Disruption of the coenzyme binding site and dimer interface revealed in the crystal structure of mitochondrial aldehyde dehydrogenase "Asian" variant., Larson HN, Weiner H, Hurley TD, J Biol Chem. 2005 Aug 26;280(34):30550-6. Epub 2005 Jun 27. PMID:15983043
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