1f17: Difference between revisions

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-[[Image:1f17.gif|left|200px]]
- {{Structure
+==L-3-HYDROXYACYL-COA DEHYDROGENASE COMPLEXED WITH NADH==
-|PDB= 1f17 |SIZE=350|CAPTION= <scene name='initialview01'>1f17</scene>, resolution 2.30&Aring;
+<StructureSection load='1f17' size='340' side='right'caption='[[1f17]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE'>NAI</scene>
+<table><tr><td colspan='2'>[[1f17]] 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=1F17 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F17 FirstGlance]. <br>
-|ACTIVITY= [http://en.wikipedia.org/wiki/3-hydroxyacyl-CoA_dehydrogenase 3-hydroxyacyl-CoA dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.35 1.1.1.35]
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
-|GENE=
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</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=1f17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f17 OCA], [https://pdbe.org/1f17 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f17 RCSB], [https://www.ebi.ac.uk/pdbsum/1f17 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f17 ProSAT]</span></td></tr>
+</table>
+== 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>
+== 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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f1/1f17_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1f17 ConSurf].
+<div style="clear:both"></div>
-'''L-3-HYDROXYACYL-COA DEHYDROGENASE COMPLEXED WITH NADH'''
+==See Also==
+*[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]]
+== References ==
-==Overview==
+<references/>
-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.
+__TOC__
+</StructureSection>
-==Disease==
-Known diseases associated with this structure: 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300256 300256]], 3-hydroxyacyl-CoA dehydrogenase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601609 601609]], Hyperinsulinemic hypoglycemia, familial, 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601609 601609]]
-==About this Structure==
-F17 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F17 OCA].
-==Reference==
-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:[http://www.ncbi.nlm.nih.gov/pubmed/10840044 10840044]
-[[Category: 3-hydroxyacyl-CoA dehydrogenase]]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[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: NAI]]
-[[Category: l-3-hydroxyacyl-coa dehydrogenase complexed with nadh]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:03:03 2008''