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4cql

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Revision as of 09:48, 20 March 2019

Crystal structure of heterotetrameric human ketoacyl reductase complexed with NAD

Structural highlights

4cql is a 16 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4cqm
Activity:	[acyl-carrier-protein_reductase 3-oxoacyl-[acyl-carrier-protein] reductase], with EC number 1.1.1.100
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ohno S, Nishikawa K, Honda Y, Nakajin S. Expression in E. coli and tissue distribution of the human homologue of the mouse Ke 6 gene, 17beta-hydroxysteroid dehydrogenase type 8. Mol Cell Biochem. 2008 Feb;309(1-2):209-15. Epub 2007 Nov 3. PMID:17978863 doi:http://dx.doi.org/10.1007/s11010-007-9637-9
↑ Chen Z, Kastaniotis AJ, Miinalainen IJ, Rajaram V, Wierenga RK, Hiltunen JK. 17beta-hydroxysteroid dehydrogenase type 8 and carbonyl reductase type 4 assemble as a ketoacyl reductase of human mitochondrial FAS. FASEB J. 2009 Nov;23(11):3682-91. Epub 2009 Jul 1. PMID:19571038 doi:http://dx.doi.org/fj.09-133587
↑ Endo S, Matsunaga T, Kitade Y, Ohno S, Tajima K, El-Kabbani O, Hara A. Human carbonyl reductase 4 is a mitochondrial NADPH-dependent quinone reductase. Biochem Biophys Res Commun. 2008 Dec 26;377(4):1326-30. doi:, 10.1016/j.bbrc.2008.11.003. Epub 2008 Nov 10. PMID:19000905 doi:http://dx.doi.org/10.1016/j.bbrc.2008.11.003
↑ Chen Z, Kastaniotis AJ, Miinalainen IJ, Rajaram V, Wierenga RK, Hiltunen JK. 17beta-hydroxysteroid dehydrogenase type 8 and carbonyl reductase type 4 assemble as a ketoacyl reductase of human mitochondrial FAS. FASEB J. 2009 Nov;23(11):3682-91. Epub 2009 Jul 1. PMID:19571038 doi:http://dx.doi.org/fj.09-133587
↑ Venkatesan R, Sah-Teli SK, Awoniyi LO, Jiang G, Prus P, Kastaniotis AJ, Hiltunen JK, Wierenga RK, Chen Z. Insights into mitochondrial fatty acid synthesis from the structure of heterotetrameric 3-ketoacyl-ACP reductase/3R-hydroxyacyl-CoA dehydrogenase. Nat Commun. 2014 Sep 9;5:4805. doi: 10.1038/ncomms5805. PMID:25203508 doi:http://dx.doi.org/10.1038/ncomms5805

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4cql"

@@ Line 1: / Line 1: @@
 ==Crystal structure of heterotetrameric human ketoacyl reductase complexed with NAD==
-<StructureSection load='4cql' size='340' side='right' caption='[[4cql]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
+<StructureSection load='4cql' size='340' side='right'caption='[[4cql]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
 == 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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cqm|4cqm]]</td></tr>
@@ Line 22: / Line 22: @@
 ==See Also==
+*[[Carbonyl reductase|Carbonyl reductase]]
 *[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]]
 == References ==
@@ Line 27: / Line 28: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Awoniyi, L O]]
 [[Category: Chen, Z]]

4cql

From Proteopedia

Revision as of 09:48, 20 March 2019

Crystal structure of heterotetrameric human ketoacyl reductase complexed with NAD

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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