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<StructureSection load='1f0y' size='340' side='right'caption='[[1f0y]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='1f0y' size='340' side='right'caption='[[1f0y]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1f0y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F0Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F0Y FirstGlance]. <br>
<table><tr><td colspan='2'>[[1f0y]] is a 2 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=1F0Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F0Y FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAA:ACETOACETYL-COENZYME+A'>CAA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3had|3had]], [[1f12|1f12]], [[1f14|1f14]], [[1f17|1f17]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAA:ACETOACETYL-COENZYME+A'>CAA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/3-hydroxyacyl-CoA_dehydrogenase 3-hydroxyacyl-CoA dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.35 1.1.1.35] </span></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=1f0y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f0y OCA], [https://pdbe.org/1f0y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f0y RCSB], [https://www.ebi.ac.uk/pdbsum/1f0y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f0y ProSAT]</span></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=1f0y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f0y OCA], [https://pdbe.org/1f0y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f0y RCSB], [https://www.ebi.ac.uk/pdbsum/1f0y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f0y ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[https://www.uniprot.org/uniprot/HCDH_HUMAN HCDH_HUMAN]] Defects in HADH are the cause of 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency (HADH deficiency) [MIM:[https://omim.org/entry/231530 231530]]. HADH deficiency is a metabolic disorder with various clinical presentations including hypoglycemia, hepatoencephalopathy, myopathy or cardiomyopathy, and in some cases sudden death.  Defects in HADH are the cause of familial hyperinsulinemic hypoglycemia type 4 (HHF4) [MIM:[https://omim.org/entry/609975 609975]]; also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or congenital hyperinsulinism. HHF is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. It causes nesidioblastosis, a diffuse abnormality of the pancreas in which there is extensive, often disorganized formation of new islets. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF4 should be easily recognizable by analysis of acylcarnitine species and that this disorder responds well to treatment with diazoxide. It provides the first 'experiment of nature' that links impaired fatty acid oxidation to hyperinsulinism and that provides support for the concept that a lipid signaling pathway is implicated in the control of insulin secretion.<ref>PMID:11489939</ref>
[https://www.uniprot.org/uniprot/HCDH_HUMAN HCDH_HUMAN] Defects in HADH are the cause of 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency (HADH deficiency) [MIM:[https://omim.org/entry/231530 231530]. HADH deficiency is a metabolic disorder with various clinical presentations including hypoglycemia, hepatoencephalopathy, myopathy or cardiomyopathy, and in some cases sudden death.  Defects in HADH are the cause of familial hyperinsulinemic hypoglycemia type 4 (HHF4) [MIM:[https://omim.org/entry/609975 609975]; also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or congenital hyperinsulinism. HHF is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. It causes nesidioblastosis, a diffuse abnormality of the pancreas in which there is extensive, often disorganized formation of new islets. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF4 should be easily recognizable by analysis of acylcarnitine species and that this disorder responds well to treatment with diazoxide. It provides the first 'experiment of nature' that links impaired fatty acid oxidation to hyperinsulinism and that provides support for the concept that a lipid signaling pathway is implicated in the control of insulin secretion.<ref>PMID:11489939</ref>  
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/HCDH_HUMAN HCDH_HUMAN]] Plays an essential role in the mitochondrial beta-oxidation of short chain fatty acids. Exerts it highest activity toward 3-hydroxybutyryl-CoA.  
[https://www.uniprot.org/uniprot/HCDH_HUMAN HCDH_HUMAN] Plays an essential role in the mitochondrial beta-oxidation of short chain fatty acids. Exerts it highest activity toward 3-hydroxybutyryl-CoA.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1f0y ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1f0y ConSurf].
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== Publication Abstract from PubMed ==
l-3-Hydroxyacyl-CoA dehydrogenase reversibly catalyzes the conversion of l-3-hydroxyacyl-CoA to 3-ketoacyl-CoA concomitant with the reduction of NAD(+) to NADH as part of the beta-oxidation spiral. In this report, crystal structures have been solved for the apoenzyme, binary complexes of the enzyme with reduced cofactor or 3-hydroxybutyryl-CoA substrate, and an abortive ternary complex of the enzyme with NAD(+) and acetoacetyl-CoA. The models illustrate positioning of cofactor and substrate within the active site of the enzyme. Comparison of these structures with the previous model of the enzyme-NAD(+) complex reveals that although significant shifting of the NAD(+)-binding domain relative to the C-terminal domain occurs in the ternary and substrate-bound complexes, there are few differences between the apoenzyme and cofactor-bound complexes. Analysis of these models clarifies the role of key amino acids implicated in catalysis and highlights additional critical residues. Furthermore, a novel charge transfer complex has been identified in the course of abortive ternary complex formation, and its characterization provides additional insight into aspects of the catalytic mechanism of l-3-hydroxyacyl-CoA dehydrogenase.
Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase.,Barycki JJ, O'Brien LK, Strauss AW, Banaszak LJ J Biol Chem. 2000 Sep 1;275(35):27186-96. PMID:10840044<ref>PMID:10840044</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1f0y" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: 3-hydroxyacyl-CoA dehydrogenase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Banaszak, L J]]
[[Category: Banaszak LJ]]
[[Category: Barycki, J J]]
[[Category: Barycki JJ]]
[[Category: Brien, L K.O]]
[[Category: O'Brien LK]]
[[Category: Strauss, A W]]
[[Category: Strauss AW]]
[[Category: Abortive ternary complex]]
[[Category: Oxidoreductase]]

Latest revision as of 07:09, 7 February 2024

L-3-HYDROXYACYL-COA DEHYDROGENASE COMPLEXED WITH ACETOACETYL-COA AND NAD+

1f0y, resolution 1.80Å

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