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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CQL FirstGlance]. <br> | <table><tr><td colspan='2'>[[4cql]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CQL FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cqm|4cqm]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cqm|4cqm]]</td></tr> | ||
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==See Also== | ==See Also== | ||
*[[Carbonyl reductase|Carbonyl reductase]] | |||
*[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]] | *[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]] | ||
== References == | == References == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Awoniyi, L O]] | [[Category: Awoniyi, L O]] | ||
[[Category: Chen, Z]] | [[Category: Chen, Z]] | ||
Revision as of 12:48, 20 March 2019
Crystal structure of heterotetrameric human ketoacyl reductase complexed with NADCrystal structure of heterotetrameric human ketoacyl reductase complexed with NAD
Structural highlights
Function[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.[1] [2] [CBR4_HUMAN] The heteroteramer with HSD17B8 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity. May play a role in biosynthesis of fatty acids in mitochondria. The homotetramer may act as NADPH-dependent quinone reductase. Has broad substrate specificity and reduces 9,10-phenanthrenequinone, 1,4-benzoquinone and various other o-quinones and p-quinones (in vitro).[3] [4] Publication Abstract from PubMedMitochondrial 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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