4g6h: Difference between revisions
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==Crystal structure of NDH with NADH== | |||
<StructureSection load='4g6h' size='340' side='right'caption='[[4g6h]], [[Resolution|resolution]] 2.26Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4g6h]] 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=4G6H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G6H FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.262Å</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=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene></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=4g6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g6h OCA], [https://pdbe.org/4g6h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g6h RCSB], [https://www.ebi.ac.uk/pdbsum/4g6h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g6h ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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 4g6h" style="background-color:#fffaf0;"></div> | ||
[[Category: Saccharomyces cerevisiae | == References == | ||
[[Category: Feng | <references/> | ||
[[Category: Ge | __TOC__ | ||
[[Category: Li | </StructureSection> | ||
[[Category: Yang | [[Category: Large Structures]] | ||
[[Category: Saccharomyces cerevisiae S288C]] | |||
[[Category: Feng Y]] | |||
[[Category: Ge J]] | |||
[[Category: Li W]] | |||
[[Category: Yang M]] | |||
Latest revision as of 16:56, 8 November 2023
Crystal structure of NDH with NADHCrystal structure of NDH with NADH
Structural highlights
FunctionNDI1_YEAST Catalyzes the oxidation of NADH generated inside the Mitochondrion. Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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