5j5z
From Proteopedia
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==Crystal structure of the D444V disease-causing mutant of the human dihydrolipoamide dehydrogenase== | ==Crystal structure of the D444V disease-causing mutant of the human dihydrolipoamide dehydrogenase== | ||
| - | <StructureSection load='5j5z' size='340' side='right' caption='[[5j5z]], [[Resolution|resolution]] 1.84Å' scene=''> | + | <StructureSection load='5j5z' size='340' side='right'caption='[[5j5z]], [[Resolution|resolution]] 1.84Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5j5z]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5J5Z OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5j5z]] 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=5J5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J5Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.84Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5j5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j5z OCA], [https://pdbe.org/5j5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j5z RCSB], [https://www.ebi.ac.uk/pdbsum/5j5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j5z ProSAT]</span></td></tr> |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/DLDH_HUMAN DLDH_HUMAN] Note=Defects in DLD are involved in the development of congenital infantile lactic acidosis. Defects in DLD are a cause of maple syrup urine disease (MSUD) [MIM:[https://omim.org/entry/248600 248600]. MSUD is characterized by mental and physical retardation, feeding problems and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine, resulting from a block in oxidative decarboxylation. |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/DLDH_HUMAN DLDH_HUMAN] Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction. |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | We report the crystal structures of the human (dihydro)lipoamide dehydrogenase (hLADH, hE3) and its disease-causing homodimer interface mutant D444V-hE3 at 2.27 and 1.84A resolution, respectively. The wild type structure is a unique uncomplexed, unliganded hE3 structure with the true canonical sequence. Based on the structural information a novel molecular pathomechanism is proposed for the impaired catalytic activity and enhanced capacity for reactive oxygen species generation of the pathogenic mutant. The mechanistic model involves a previously much ignored solvent accessible channel leading to the active site that might be perturbed also by other disease-causing homodimer interface substitutions of this enzyme. | ||
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| + | Crystal structures of the disease-causing D444V mutant and the relevant wild type human dihydrolipoamide dehydrogenase.,Szabo E, Mizsei R, Wilk P, Zambo Z, Torocsik B, Weiss MS, Adam-Vizi V, Ambrus A Free Radic Biol Med. 2018 Jun 20;124:214-220. doi:, 10.1016/j.freeradbiomed.2018.06.008. PMID:29908278<ref>PMID:29908278</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5j5z" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Dihydrolipoamide dehydrogenase|Dihydrolipoamide dehydrogenase]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: Adam-Vizi | + | [[Category: Large Structures]] |
| - | [[Category: Ambrus | + | [[Category: Adam-Vizi V]] |
| - | [[Category: Mizsei | + | [[Category: Ambrus A]] |
| - | [[Category: Szabo | + | [[Category: Mizsei R]] |
| - | [[Category: Torocsik | + | [[Category: Szabo E]] |
| - | [[Category: Weiss | + | [[Category: Torocsik B]] |
| - | [[Category: Zambo | + | [[Category: Weiss MS]] |
| - | + | [[Category: Zambo Z]] | |
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Current revision
Crystal structure of the D444V disease-causing mutant of the human dihydrolipoamide dehydrogenase
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Categories: Homo sapiens | Large Structures | Adam-Vizi V | Ambrus A | Mizsei R | Szabo E | Torocsik B | Weiss MS | Zambo Z
