View source for 4qgk


==Structure of the Human Sjogren Larsson Syndrome enzyme fatty aldehyde dehydrogenase (FALDH)==
<StructureSection load='4qgk' size='340' side='right'caption='[[4qgk]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4qgk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QGK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QGK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qgk OCA], [https://pdbe.org/4qgk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qgk RCSB], [https://www.ebi.ac.uk/pdbsum/4qgk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qgk ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/AL3A2_HUMAN AL3A2_HUMAN] Sjogren-Larsson syndrome. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:8528251</ref> <ref>PMID:9254849</ref> <ref>PMID:9829906</ref> <ref>PMID:10577908</ref> <ref>PMID:10792573</ref> 
== Function ==
[https://www.uniprot.org/uniprot/AL3A2_HUMAN AL3A2_HUMAN] Catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length. Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid.<ref>PMID:22633490</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mutations in the gene coding for membrane-bound fatty aldehyde dehydrogenase (FALDH) lead to toxic accumulation of lipid species and development of the Sjogren-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.

A gatekeeper helix determines the substrate specificity of Sjogren-Larsson Syndrome enzyme fatty aldehyde dehydrogenase.,Keller MA, Zander U, Fuchs JE, Kreutz C, Watschinger K, Mueller T, Golderer G, Liedl KR, Ralser M, Krautler B, Werner ER, Marquez JA Nat Commun. 2014 Jul 22;5:4439. doi: 10.1038/ncomms5439. PMID:25047030<ref>PMID:25047030</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4qgk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Keller M]]
[[Category: Marquez JA]]
[[Category: Zander U]]