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1x80

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[[Image:1x80.png|left|200px]]
 
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{{STRUCTURE_1x80| PDB=1x80 | SCENE= }}
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==Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase==
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<StructureSection load='1x80' size='340' side='right'caption='[[1x80]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1x80]] 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=1X80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X80 FirstGlance]. <br>
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</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&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1x80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x80 OCA], [https://pdbe.org/1x80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x80 RCSB], [https://www.ebi.ac.uk/pdbsum/1x80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x80 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/ODBA_HUMAN ODBA_HUMAN] Defects in BCKDHA are a cause of maple syrup urine disease type IA (MSUD1A) [MIM:[https://omim.org/entry/248600 248600]. MSUD is an autosomal recessive disorder characterized by mental and physical retardation, feeding problems, and a maple syrup odor to the urine.<ref>PMID:2060625</ref> <ref>PMID:8037208</ref> <ref>PMID:2703538</ref> <ref>PMID:2241958</ref> <ref>PMID:1867199</ref> <ref>PMID:1885764</ref> <ref>PMID:8161368</ref> <ref>PMID:7883996</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/ODBA_HUMAN ODBA_HUMAN] The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x8/1x80_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1x80 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) is a 4 MDa macromolecular machine comprising three catalytic components (E1b, E2b, and E3), a kinase, and a phosphatase. The BCKDC overall activity is tightly regulated by phosphorylation in response to hormonal and dietary stimuli. We report that phosphorylation of Ser292-alpha in the E1b active site channel results in an order-to-disorder transition of the conserved phosphorylation loop carrying the phosphoryl serine. The conformational change is triggered by steric clashes of the phosphoryl group with invariant His291-alpha that serves as an indispensable anchor for the phosphorylation loop through bound thiamin diphosphate. Phosphorylation of Ser292-alpha does not severely impede the E1b-dependent decarboxylation of alpha-ketoacids. However, the disordered loop conformation prevents phosphorylated E1b from binding the E2b lipoyl-bearing domain, which effectively shuts off the E1b-catalyzed reductive acylation reaction and therefore completely inactivates BCKDC. This mechanism provides a paradigm for regulation of mitochondrial alpha-ketoacid dehydrogenase complexes by phosphorylation.
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===Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase===
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Molecular mechanism for regulation of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex by phosphorylation.,Wynn RM, Kato M, Machius M, Chuang JL, Li J, Tomchick DR, Chuang DT Structure. 2004 Dec;12(12):2185-96. PMID:15576032<ref>PMID:15576032</ref>
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{{ABSTRACT_PUBMED_15576032}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1x80" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[1x80]] is a 2 chain structure with 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=1X80 OCA].
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*[[2-oxoisovalerate dehydrogenase|2-oxoisovalerate dehydrogenase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:015576032</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Chuang, D T.]]
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[[Category: Large Structures]]
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[[Category: Chuang, J L.]]
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[[Category: Chuang DT]]
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[[Category: Kato, M.]]
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[[Category: Chuang JL]]
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[[Category: Li, J.]]
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[[Category: Kato M]]
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[[Category: Machius, M.]]
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[[Category: Li J]]
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[[Category: Tomchick, D R.]]
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[[Category: Machius M]]
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[[Category: Wynn, R M.]]
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[[Category: Tomchick DR]]
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[[Category: Acylation]]
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[[Category: Wynn RM]]
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[[Category: Branched-chain]]
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[[Category: Flavoprotein]]
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[[Category: Ketoacid dehydrogenase]]
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[[Category: Multi-enzyme complex]]
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[[Category: Oxidative decarboxylation maple syrup urine disease]]
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[[Category: Oxidoreductase]]
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[[Category: Phosphorylation]]
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[[Category: Thiamin diphosphate]]
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Current revision

Crystal structure of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase

PDB ID 1x80

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