|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of NDH with TRT== | | ==Crystal structure of NDH with TRT== |
| - | <StructureSection load='4g6g' size='340' side='right' caption='[[4g6g]], [[Resolution|resolution]] 2.39Å' scene=''> | + | <StructureSection load='4g6g' size='340' side='right'caption='[[4g6g]], [[Resolution|resolution]] 2.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4g6g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G6G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G6G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4g6g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G6G 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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TRT:FRAGMENT+OF+TRITON+X-100'>TRT</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]] 2.39Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g6h|4g6h]], [[4g73|4g73]], [[4g74|4g74]]</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TRT:FRAGMENT+OF+TRITON+X-100'>TRT</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NDI1, YML120C, YM7056.06C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=4g6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g6g OCA], [https://pdbe.org/4g6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g6g RCSB], [https://www.ebi.ac.uk/pdbsum/4g6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g6g ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NADH:ubiquinone_reductase_(non-electrogenic) NADH:ubiquinone reductase (non-electrogenic)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.5.9 1.6.5.9] </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=4g6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g6g OCA], [http://pdbe.org/4g6g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g6g RCSB], [http://www.ebi.ac.uk/pdbsum/4g6g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g6g ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NDI1_YEAST NDI1_YEAST]] Catalyzes the oxidation of NADH generated inside the Mitochondrion. | + | [https://www.uniprot.org/uniprot/NDI1_YEAST NDI1_YEAST] Catalyzes the oxidation of NADH generated inside the Mitochondrion. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The single-component type-II NADH dehydrogenases (NDH-2s) serve as alternatives to the multisubunit respiratory complex I (type-I NADH dehydrogenase (NDH-1), also called NADH:ubiquinone oxidoreductase; EC 1.6.5.3) in catalysing electron transfer from NADH to ubiquinone in the mitochondrial respiratory chain. The yeast NDH-2 (Ndi1) oxidizes NADH on the matrix side and reduces ubiquinone to maintain mitochondrial NADH/NAD(+) homeostasis. Ndi1 is a potential therapeutic agent for human diseases caused by complex I defects, particularly Parkinson's disease, because its expression restores the mitochondrial activity in animals with complex I deficiency. NDH-2s in pathogenic microorganisms are viable targets for new antibiotics. Here we solve the crystal structures of Ndi1 in its substrate-free, NADH-, ubiquinone- and NADH-ubiquinone-bound states, to help understand the catalytic mechanism of NDH-2s. We find that Ndi1 homodimerization through its carboxy-terminal domain is critical for its catalytic activity and membrane targeting. The structures reveal two ubiquinone-binding sites (UQ(I) and UQ(II)) in Ndi1. NADH and UQ(I) can bind to Ndi1 simultaneously to form a substrate-protein complex. We propose that UQ(I) interacts with FAD to act as an intermediate for electron transfer, and that NADH transfers electrons through this FAD-UQ(I) complex to UQ(II). Together our data reveal the regulatory and catalytic mechanisms of Ndi1 and may facilitate the development or targeting of NDH-2s for potential therapeutic applications.
| + | |
| - | | + | |
| - | Structural insight into the type-II mitochondrial NADH dehydrogenases.,Feng Y, Li W, Li J, Wang J, Ge J, Xu D, Liu Y, Wu K, Zeng Q, Wu JW, Tian C, Zhou B, Yang M Nature. 2012 Nov 15;491(7424):478-82. doi: 10.1038/nature11541. Epub 2012 Oct 21. PMID:23086143<ref>PMID:23086143</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4g6g" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | + | [[Category: Large Structures]] |
| - | [[Category: Feng, Y]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Ge, J]] | + | [[Category: Feng Y]] |
| - | [[Category: Li, W]] | + | [[Category: Ge J]] |
| - | [[Category: Yang, M]] | + | [[Category: Li W]] |
| - | [[Category: Electron transfer]]
| + | [[Category: Yang M]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| - | [[Category: Trt]]
| + | |
