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| | ==Crystal Structure of the Dihydrolipoamide Dehydrogenase (E3)-Binding Domain of Human E3-Binding Protein== | | ==Crystal Structure of the Dihydrolipoamide Dehydrogenase (E3)-Binding Domain of Human E3-Binding Protein== |
| - | <StructureSection load='2f60' size='340' side='right' caption='[[2f60]], [[Resolution|resolution]] 1.55Å' scene=''> | + | <StructureSection load='2f60' size='340' side='right'caption='[[2f60]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2f60]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F60 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2F60 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2f60]] is a 1 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=2F60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F60 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.55Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2f5z|2f5z]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDHX, PDX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2f60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f60 OCA], [https://pdbe.org/2f60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f60 RCSB], [https://www.ebi.ac.uk/pdbsum/2f60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f60 ProSAT]</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=2f60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f60 OCA], [http://pdbe.org/2f60 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2f60 RCSB], [http://www.ebi.ac.uk/pdbsum/2f60 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2f60 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ODPX_HUMAN ODPX_HUMAN]] Defects in PDHX are the cause of pyruvate dehydrogenase E3-binding protein deficiency (PDHXD) [MIM:[http://omim.org/entry/245349 245349]].<ref>PMID:9399911</ref> | + | [https://www.uniprot.org/uniprot/ODPX_HUMAN ODPX_HUMAN] Defects in PDHX are the cause of pyruvate dehydrogenase E3-binding protein deficiency (PDHXD) [MIM:[https://omim.org/entry/245349 245349].<ref>PMID:9399911</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ODPX_HUMAN ODPX_HUMAN]] Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex. | + | [https://www.uniprot.org/uniprot/ODPX_HUMAN ODPX_HUMAN] Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Pyruvate dehydrogenase|Pyruvate dehydrogenase]] | + | *[[Pyruvate dehydrogenase 3D structures|Pyruvate dehydrogenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Brautigam, C A]] | + | [[Category: Large Structures]] |
| - | [[Category: Chuang, D T]] | + | [[Category: Brautigam CA]] |
| - | [[Category: Chuang, J L]] | + | [[Category: Chuang DT]] |
| - | [[Category: Machius, M]] | + | [[Category: Chuang JL]] |
| - | [[Category: Tomchick, D R]] | + | [[Category: Machius M]] |
| - | [[Category: Wynn, R M]]
| + | [[Category: Tomchick DR]] |
| - | [[Category: E3bd]] | + | [[Category: Wynn RM]] |
| - | [[Category: Protein binding]] | + | |
| - | [[Category: Protein-binding protein]]
| + | |
| Structural highlights
Disease
ODPX_HUMAN Defects in PDHX are the cause of pyruvate dehydrogenase E3-binding protein deficiency (PDHXD) [MIM:245349.[1]
Function
ODPX_HUMAN Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The 9.5 MDa human pyruvate dehydrogenase complex (PDC) utilizes the specific dihydrolipoamide dehydrogenase (E3) binding protein (E3BP) to tether the essential E3 component to the 60-meric core of the complex. Here, we report crystal structures of the binding domain (E3BD) of human E3BP alone and in complex with human E3 at 1.6 angstroms and 2.2 angstroms, respectively. The latter structure shows that residues from E3BD contact E3 across its 2-fold axis, resulting in one E3BD binding site on the E3 homodimer. Negligible conformational changes occur in E3BD upon its high-affinity binding to E3. Modifications of E3BD residues at the center of the E3BD/E3 interface impede E3 binding far more severely than those of residues on the periphery, validating the "hot spot" paradigm for protein interactions. A cluster of disease-causing E3 mutations located near the center of the E3BD/E3 interface prevents the efficient recruitment of these E3 variants by E3BP into the PDC, leading to the dysfunction of the PDC catalytic machine.
Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex.,Brautigam CA, Wynn RM, Chuang JL, Machius M, Tomchick DR, Chuang DT Structure. 2006 Mar;14(3):611-21. Epub 2006 Jan 26. PMID:16442803[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Aral B, Benelli C, Ait-Ghezala G, Amessou M, Fouque F, Maunoury C, Creau N, Kamoun P, Marsac C. Mutations in PDX1, the human lipoyl-containing component X of the pyruvate dehydrogenase-complex gene on chromosome 11p1, in congenital lactic acidosis. Am J Hum Genet. 1997 Dec;61(6):1318-26. PMID:9399911 doi:S0002-9297(07)60233-X
- ↑ Brautigam CA, Wynn RM, Chuang JL, Machius M, Tomchick DR, Chuang DT. Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex. Structure. 2006 Mar;14(3):611-21. Epub 2006 Jan 26. PMID:16442803 doi:10.1016/j.str.2006.01.001
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