4cql: Difference between revisions
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==Crystal structure of heterotetrameric human ketoacyl reductase complexed with NAD== | ==Crystal structure of heterotetrameric human ketoacyl reductase complexed with NAD== | ||
<StructureSection load='4cql' size='340' side='right' caption='[[4cql]], [[Resolution|resolution]] 2.85Å' scene=''> | <StructureSection load='4cql' size='340' side='right'caption='[[4cql]], [[Resolution|resolution]] 2.85Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4cql]] is a 16 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CQL OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4cql]] is a 16 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=4CQL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CQL FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | |||
<tr><td class="sblockLbl"><b> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4cql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cql OCA], [https://pdbe.org/4cql PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cql RCSB], [https://www.ebi.ac.uk/pdbsum/4cql PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cql ProSAT]</span></td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </table> | ||
<table> | == Function == | ||
[https://www.uniprot.org/uniprot/DHB8_HUMAN DHB8_HUMAN] NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol. Has very low activity towards testosterone. The heteroteramer with CBR4 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity. May play a role in biosynthesis of fatty acids in mitochondria.<ref>PMID:17978863</ref> <ref>PMID:19571038</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mitochondrial fatty acid synthesis (mtFAS) is essential for respiratory growth in yeast and mammalian embryonic survival. The human 3-ketoacyl-acyl carrier protein (ACP) reductase (KAR) of mtFAS is a heterotetrameric alpha2beta2-assembly composed of 17beta-hydroxysteroid dehydrogenase type-8 (HSD17B8, alpha-subunit) and carbonyl reductase type-4 (CBR4, beta-subunit). Here we provide a structural explanation for the stability of the heterotetramer from the crystal structure with NAD(+) and NADP(+) bound to the HSD17B8 and CBR4 subunits, respectively, and show that the catalytic activity of the NADPH- and ACP-dependent CBR4 subunit is crucial for a functional HsKAR. Therefore, mtFAS is NADPH- and ACP dependent, employing the 3R-hydroxyacyl-ACP intermediate. HSD17B8 assists in the formation of the competent HsKAR assembly. The intrinsic NAD(+)- and CoA-dependent activity of the HSD17B8 subunit on the 3R-hydroxyacyl-CoA intermediates may indicate a role for this subunit in routing 3R-hydroxyacyl-CoA esters, potentially arising from the metabolism of unsaturated fatty acids, into the mitochondrial beta-oxidation pathway. | |||
Insights into mitochondrial fatty acid synthesis from the structure of heterotetrameric 3-ketoacyl-ACP reductase/3R-hydroxyacyl-CoA dehydrogenase.,Venkatesan R, Sah-Teli SK, Awoniyi LO, Jiang G, Prus P, Kastaniotis AJ, Hiltunen JK, Wierenga RK, Chen Z Nat Commun. 2014 Sep 9;5:4805. doi: 10.1038/ncomms5805. PMID:25203508<ref>PMID:25203508</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4cql" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Carbonyl reductase 3D structures|Carbonyl reductase 3D structures]] | |||
*[[Hydroxysteroid dehydrogenase 3D structures|Hydroxysteroid dehydrogenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Awoniyi | [[Category: Homo sapiens]] | ||
[[Category: Chen | [[Category: Large Structures]] | ||
[[Category: Hiltunen | [[Category: Awoniyi LO]] | ||
[[Category: Jiang | [[Category: Chen Z]] | ||
[[Category: Kastaniotis | [[Category: Hiltunen JK]] | ||
[[Category: Prus | [[Category: Jiang G]] | ||
[[Category: Sah-Teli | [[Category: Kastaniotis AJ]] | ||
[[Category: Venkatesan | [[Category: Prus P]] | ||
[[Category: Wierenga | [[Category: Sah-Teli SK]] | ||
[[Category: Venkatesan R]] | |||
[[Category: Wierenga RK]] | |||
