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| | <StructureSection load='5l46' size='340' side='right'caption='[[5l46]], [[Resolution|resolution]] 3.09Å' scene=''> | | <StructureSection load='5l46' size='340' side='right'caption='[[5l46]], [[Resolution|resolution]] 3.09Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5l46]] is a 2 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=5L46 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5L46 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5l46]] 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=5L46 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L46 FirstGlance]. <br> |
| - | </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></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]] 3.09Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DMGDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dimethylglycine_dehydrogenase Dimethylglycine dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.8.4 1.5.8.4] </span></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=5l46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l46 OCA], [https://pdbe.org/5l46 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l46 RCSB], [https://www.ebi.ac.uk/pdbsum/5l46 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l46 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5l46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l46 OCA], [http://pdbe.org/5l46 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l46 RCSB], [http://www.ebi.ac.uk/pdbsum/5l46 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l46 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/M2GD_HUMAN M2GD_HUMAN]] Dimethylglycine dehydrogenase deficiency. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/M2GD_HUMAN M2GD_HUMAN] Dimethylglycine dehydrogenase deficiency. The disease is caused by mutations affecting the gene represented in this entry. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/M2GD_HUMAN M2GD_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dimethylglycine dehydrogenase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gruber, K]] | + | [[Category: Gruber K]] |
| - | [[Category: Hromic, A]] | + | [[Category: Hromic A]] |
| - | [[Category: Pavkov-Keller, T]] | + | [[Category: Pavkov-Keller T]] |
| - | [[Category: Covalent flavinylation]]
| + | |
| - | [[Category: Electron transfer]]
| + | |
| - | [[Category: One-carbon metabolism]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Disease
M2GD_HUMAN Dimethylglycine dehydrogenase deficiency. The disease is caused by mutations affecting the gene represented in this entry.
Function
M2GD_HUMAN
Publication Abstract from PubMed
The human dimethylglycine dehydrogenase (hDMGDH) is a flavin adenine dinucleotide (FAD)- and tetrahydrofolate (THF)-dependent, mitochondrial matrix enzyme taking part in choline degradation, one-carbon metabolism and electron transfer to the respiratory chain. The rare natural variant H109R causes dimethylglycine dehydrogenase deficiency leading to increased blood and urinary dimethylglycine concentrations. A detailed biochemical and structural characterization of hDMGDH was thus far hampered by insufficient heterologous expression of the protein. In the present study, we report the development of an intracellular, heterologous expression system in Komagataella phaffii (formerly known as Pichia pastoris) providing the opportunity to determine kinetic parameters, spectroscopic properties, thermostability, and the redox potential of hDMGDH. Moreover, we have successfully crystallized the wild-type enzyme and determined the structure to 3.1-A resolution. The structure-based analysis of our biochemical data provided new insights into the kinetic properties of the enzyme in particular with respect to oxygen reactivity. A comparative study with the H109R variant demonstrated that the variant suffers from decreased protein stability, cofactor saturation, and substrate affinity. DATABASE: Structural data are available in the PDB database under the accession number 5L46.
Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease-related H109R variant.,Augustin P, Hromic A, Pavkov-Keller T, Gruber K, Macheroux P FEBS J. 2016 Aug 3. doi: 10.1111/febs.13828. PMID:27486859[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Augustin P, Hromic A, Pavkov-Keller T, Gruber K, Macheroux P. Structure and biochemical properties of recombinant human dimethylglycine dehydrogenase and comparison to the disease-related H109R variant. FEBS J. 2016 Aug 3. doi: 10.1111/febs.13828. PMID:27486859 doi:http://dx.doi.org/10.1111/febs.13828
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