1zum

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{{STRUCTURE_1zum| PDB=1zum | SCENE= }}
{{STRUCTURE_1zum| PDB=1zum | SCENE= }}
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'''Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, Apo Form'''
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===Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, Apo Form===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 15983043 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15983043}}
==About this Structure==
==About this Structure==
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[[Category: Weiner, H.]]
[[Category: Weiner, H.]]
[[Category: Rossman fold]]
[[Category: Rossman fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:05:42 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 16:16:40 2008''

Revision as of 13:16, 27 July 2008

Image:1zum.png

Template:STRUCTURE 1zum

Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, Apo Form

Template:ABSTRACT PUBMED 15983043

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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