1zum

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spinqualitylabelsall models 1zum, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 with NA, GAI and EDO as ligands. Active as Aldehyde dehydrogenase (NAD(+)), with EC number 1.2.1.3 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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