View source for 4cqm


==Crystal structure of heterotetrameric human ketoacyl reductase complexed with NAD and NADP==
<StructureSection load='4cqm' size='340' side='right'caption='[[4cqm]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cqm]] 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=4CQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CQM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=OAS:O-ACETYLSERINE'>OAS</scene></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=4cqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cqm OCA], [https://pdbe.org/4cqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cqm RCSB], [https://www.ebi.ac.uk/pdbsum/4cqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cqm ProSAT]</span></td></tr>
</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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4cqm" 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__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Awoniyi LO]]
[[Category: Chen Z]]
[[Category: Hiltunen JK]]
[[Category: Jiang G]]
[[Category: Kastoniotis AJ]]
[[Category: Prus P]]
[[Category: SahTeli SK]]
[[Category: Venkatesan R]]
[[Category: Wierenga RK]]