4QGK

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

Summary for 4QGK

• Entry DOI: 10.2210/pdb4qgk/pdb
• Descriptor: Fatty aldehyde dehydrogenase (2 entities in total)
• Functional Keywords: aldehyde dehydrogenase, fatty aldehyde dehydrogenase, sjogren larsson syndrome, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane ; Single-pass membrane protein ; Cytoplasmic side : P51648
• Total number of polymer chains: 2
• Total formula weight: 104472.70

Authors

Zander, U.,Keller, M.,Marquez, J.A. (deposition date: 2014-05-23, release date: 2014-07-30, Last modification date: 2023-11-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.1 Å)