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New page: left|200px<br /> <applet load="1rx0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rx0, resolution 1.77Å" /> '''Crystal structure o...
 
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[[Image:1rx0.gif|left|200px]]<br />
<applet load="1rx0" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1rx0, resolution 1.77&Aring;" />
'''Crystal structure of isobutyryl-CoA dehydrogenase complexed with substrate/ligand.'''<br />


==Overview==
==Crystal structure of isobutyryl-CoA dehydrogenase complexed with substrate/ligand.==
The acyl-CoA dehydrogenases are a family of mitochondrial flavoproteins, involved in the catabolism of fatty and amino acids. Isobutyryl-CoA, dehydrogenase (IBD) is involved in the catabolism of valine and catalyzes, the conversion of isobutyryl-CoA to methacrylyl-CoA. The crystal structure, of IBD with and without substrate has been determined to 1.76-A, resolution. The asymmetric unit contains a homotetramer with, substrate/product bound in two monomers. The overall structure of IBD is, similar to those of previously determined acyl-CoA dehydrogenases and, consists of an NH2-terminal alpha-helical domain, a medial beta-strand, domain and a C-terminal alpha-helical domain. The enzyme-bound ligand has, been modeled in as the reaction product, methacrylyl-CoA. The location of, Glu-376 with respect to the C-2-C-3 of the bound product and FAD confirms, Glu-376 to be the catalytic base. IBD has a shorter and wider, substrate-binding cavity relative to short-chain acyl-CoA dehydrogenase, permitting the optimal binding of the isobutyryl-CoA substrate. The, dramatic lateral expansion of the binding cavity seen in isovaleryl-CoA, dehydrogenase is not observed in IBD. The conserved tyrosine or, phenylalanine that defines a side of the binding cavity in other acyl-CoA, dehydrogenases is replaced by a leucine (Leu-375) in the current, structure. Substrate binding changes the position of some residues lining, the binding pocket as well as the position of the loop containing the, catalytic glutamate and subsequent helix. Three clinical mutations have, been modeled to the structure. The mutations do not affect substrate, binding but instead appear to disrupt protein folding and/or stability.
<StructureSection load='1rx0' size='340' side='right'caption='[[1rx0]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1rx0]] is a 4 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=1RX0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RX0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.77&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2MC:METHACRYLYL-COENZYME+A'>2MC</scene>, <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=1rx0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rx0 OCA], [https://pdbe.org/1rx0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rx0 RCSB], [https://www.ebi.ac.uk/pdbsum/1rx0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rx0 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ACAD8_HUMAN ACAD8_HUMAN] Defects in ACAD8 are the cause of isobutyryl-CoA dehydrogenase deficiency (IBDD) [MIM:[https://omim.org/entry/611283 611283]. The symptoms of IBDD generally appear until late in infancy or in childhood and can include poor feeding and growth (failure to thrive), a weakened and enlarged heart (dilated cardiomyopathy), seizures, and low numbers of red blood cells (anemia).<ref>PMID:12359132</ref> <ref>PMID:15505379</ref> <ref>PMID:16857760</ref>
== Function ==
[https://www.uniprot.org/uniprot/ACAD8_HUMAN ACAD8_HUMAN] Has very high activity toward isobutyryl-CoA. Is an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Plays a role in transcriptional coactivation within the ARC complex.<ref>PMID:11013134</ref> <ref>PMID:12359132</ref>
== 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/rx/1rx0_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=1rx0 ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known diseases associated with this structure: Blau syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605956 605956]], Crohn disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605956 605956]], Isobutyryl-CoA dehydrogenase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604773 604773]], Psoriatic arthritis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605956 605956]], Sarcoidosis, early-onset OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605956 605956]]
*[[Acyl-CoA dehydrogenase 3D structures|Acyl-CoA dehydrogenase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1RX0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with EDO, FAD, 2MC and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RX0 OCA].
__TOC__
 
</StructureSection>
==Reference==
Structures of isobutyryl-CoA dehydrogenase and enzyme-product complex: comparison with isovaleryl- and short-chain acyl-CoA dehydrogenases., Battaile KP, Nguyen TV, Vockley J, Kim JJ, J Biol Chem. 2004 Apr 16;279(16):16526-34. Epub 2004 Jan 28. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14752098 14752098]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Battaile, K.P.]]
[[Category: Battaile KP]]
[[Category: Kim, J.J.]]
[[Category: Kim JJ]]
[[Category: Nguyen, T.V.]]
[[Category: Nguyen TV]]
[[Category: Vockley, J.]]
[[Category: Vockley J]]
[[Category: 2MC]]
[[Category: ACY]]
[[Category: EDO]]
[[Category: FAD]]
[[Category: coenzyme a]]
[[Category: dehydrogenase]]
[[Category: flavoprotein]]
 
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