4cqm

From Proteopedia

(Difference between revisions)

Revision as of 14:03, 24 December 2014

Crystal structure of heterotetrameric human ketoacyl reductase complexed with NAD and NADP

Structural highlights

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

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 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4cqm]] is a 16 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CQM FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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></td></tr>
-<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=OAS:O-ACETYLSERINE'>OAS</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=OAS:O-ACETYLSERINE'>OAS</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cql|4cql]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cql|4cql]]</td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-oxoacyl-[acyl-carrier-protein]_reductase 3-oxoacyl-[acyl-carrier-protein] reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.100 1.1.1.100] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-oxoacyl-[acyl-carrier-protein]_reductase 3-oxoacyl-[acyl-carrier-protein] reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.100 1.1.1.100] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cqm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cqm RCSB], [http://www.ebi.ac.uk/pdbsum/4cqm PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cqm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cqm RCSB], [http://www.ebi.ac.uk/pdbsum/4cqm PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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>  [[http://www.uniprot.org/uniprot/CBR4_HUMAN 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).<ref>PMID:19000905</ref> <ref>PMID:19571038</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Awoniyi, L O.]]
+[[Category: Awoniyi, L O]]
-[[Category: Chen, Z.]]
+[[Category: Chen, Z]]
-[[Category: Hiltunen, J K.]]
+[[Category: Hiltunen, J K]]
-[[Category: Jiang, G.]]
+[[Category: Jiang, G]]
-[[Category: Kastoniotis, A J.]]
+[[Category: Kastoniotis, A J]]
-[[Category: Prus, P.]]
+[[Category: Prus, P]]
-[[Category: SahTeli, S K.]]
+[[Category: SahTeli, S K]]
-[[Category: Venkatesan, R.]]
+[[Category: Venkatesan, R]]
-[[Category: Wierenga, R K.]]
+[[Category: Wierenga, R K]]
 [[Category: 17-beta hydroxysteroid dehydrogenase]]
 [[Category: 3-ketoacyl-acp reductase]]

4cqm

From Proteopedia

Revision as of 14:03, 24 December 2014

Crystal structure of heterotetrameric human ketoacyl reductase complexed with NAD and NADP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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