4QGK

Structure of the Human Sjogren Larsson Syndrome enzyme fatty aldehyde dehydrogenase (FALDH)

4QGK の概要

• エントリーDOI: 10.2210/pdb4qgk/pdb
• 分子名称: Fatty aldehyde dehydrogenase (2 entities in total)
• 機能のキーワード: aldehyde dehydrogenase, fatty aldehyde dehydrogenase, sjogren larsson syndrome, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum membrane ; Single-pass membrane protein ; Cytoplasmic side : P51648
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 104472.70

構造登録者

Zander, U.,Keller, M.,Marquez, J.A. (登録日: 2014-05-23, 公開日: 2014-07-30, 最終更新日: 2023-11-08)

主引用文献

Keller, M.A.,Zander, U.,Fuchs, J.E.,Kreutz, C.,Watschinger, K.,Mueller, T.,Golderer, G.,Liedl, K.R.,Ralser, M.,Krautler, B.,Werner, E.R.,Marquez, J.A.
A gatekeeper helix determines the substrate specificity of Sjogren-Larsson Syndrome enzyme fatty aldehyde dehydrogenase.
Nat Commun, 5:4439-4439, 2014

PubMed Abstract: Mutations in the gene coding for membrane-bound fatty aldehyde dehydrogenase (FALDH) lead to toxic accumulation of lipid species and development of the Sjögren-Larsson Syndrome (SLS), a rare disorder characterized by skin defects and mental retardation. Here, we present the crystallographic structure of human FALDH, the first model of a membrane-associated aldehyde dehydrogenase. The dimeric FALDH displays a previously unrecognized element in its C-terminal region, a 'gatekeeper' helix, which extends over the adjacent subunit, controlling the access to the substrate cavity and helping orientate both substrate cavities towards the membrane surface for efficient substrate transit between membranes and catalytic site. Activity assays demonstrate that the gatekeeper helix is important for directing the substrate specificity of FALDH towards long-chain fatty aldehydes. The gatekeeper feature is conserved across membrane-associated aldehyde dehydrogenases. Finally, we provide insight into the previously elusive molecular basis of SLS-causing mutations.

PubMed: 25047030
DOI: 10.1038/ncomms5439

実験手法

X-RAY DIFFRACTION (2.1 Å)