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| | <SX load='6h05' size='340' side='right' viewer='molstar' caption='[[6h05]], [[Resolution|resolution]] 2.90Å' scene=''> | | <SX load='6h05' size='340' side='right' viewer='molstar' caption='[[6h05]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6h05]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6H05 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6h05]] 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=6H05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6H05 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DLST, DLTS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.9Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Dihydrolipoyllysine-residue_succinyltransferase Dihydrolipoyllysine-residue succinyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.61 2.3.1.61] </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=6h05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h05 OCA], [https://pdbe.org/6h05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6h05 RCSB], [https://www.ebi.ac.uk/pdbsum/6h05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6h05 ProSAT]</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=6h05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h05 OCA], [https://pdbe.org/6h05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6h05 RCSB], [https://www.ebi.ac.uk/pdbsum/6h05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6h05 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ODO2_HUMAN ODO2_HUMAN]] Dihydrolipoamide succinyltransferase (E2) component of the 2-oxoglutarate dehydrogenase complex (By similarity). The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) (By similarity). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711).[UniProtKB:Q9N0F1]<ref>PMID:29211711</ref>
| + | [https://www.uniprot.org/uniprot/ODO2_HUMAN ODO2_HUMAN] Dihydrolipoamide succinyltransferase (E2) component of the 2-oxoglutarate dehydrogenase complex (By similarity). The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) (By similarity). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711).[UniProtKB:Q9N0F1]<ref>PMID:29211711</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Dihydrolipoyllysine-residue succinyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Adam-Vizi, V]] | + | [[Category: Adam-Vizi V]] |
| - | [[Category: Ambrus, A]] | + | [[Category: Ambrus A]] |
| - | [[Category: Hubert, A]] | + | [[Category: Hubert A]] |
| - | [[Category: Jordan, F]] | + | [[Category: Jordan F]] |
| - | [[Category: Nagy, B]] | + | [[Category: Nagy B]] |
| - | [[Category: Nemeria, N S]] | + | [[Category: Nemeria NS]] |
| - | [[Category: Novacek, J]] | + | [[Category: Novacek J]] |
| - | [[Category: Polak, M]] | + | [[Category: Polak M]] |
| - | [[Category: Zambo, Z]] | + | [[Category: Zambo Z]] |
| - | [[Category: 2-oxoglutarate dehydrogenase complex]]
| + | |
| - | [[Category: Alpha-ketoglutarate dehydrogenase complex]]
| + | |
| - | [[Category: Dihydrolipoamide succinyltransferase]]
| + | |
| - | [[Category: E2 component]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
ODO2_HUMAN Dihydrolipoamide succinyltransferase (E2) component of the 2-oxoglutarate dehydrogenase complex (By similarity). The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) (By similarity). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711).[UniProtKB:Q9N0F1][1]
Publication Abstract from PubMed
BACKGROUND: The human mitochondrial alpha-ketoglutarate dehydrogenase complex (hKGDHc) converts KG to succinyl-CoA and NADH. Malfunction of and reactive oxygen species generation by the hKGDHc as well as its E1-E2 subcomplex are implicated in neurodegenerative disorders, ischemia-reperfusion injury, E3-deficiency and cancers. METHODS: We performed cryo-EM, cross-linking mass spectrometry (CL-MS) and molecular modeling analyses to determine the structure of the E2 component of the hKGDHc (hE2k); hE2k transfers a succinyl group to CoA and forms the structural core of hKGDHc. We also assessed the overall structure of the hKGDHc by negative-stain EM and modeling. RESULTS: We report the 2.9A resolution cryo-EM structure of the hE2k component. The cryo-EM map comprises density for hE2k residues 151-386 - the entire (inner) core catalytic domain plus a few additional residues -, while residues 1-150 are not observed due to the inherent flexibility of the N-terminal region. The structure of the latter segment was also determined by CL-MS and homology modeling. Negative-stain EM on in vitro assembled hKGDHc and previous data were used to build a putative overall structural model of the hKGDHc. CONCLUSIONS: The E2 core of the hKGDHc is composed of 24 hE2k chains organized in octahedral (8x3 type) assembly. Each lipoyl domain is oriented towards the core domain of an adjacent chain in the hE2k homotrimer. hE1k and hE3 are most likely tethered at the edges and faces, respectively, of the cubic hE2k assembly. GENERAL SIGNIFICANCE: The revealed structural information will support the future pharmacologically targeting of the hKGDHc.
Structure of the dihydrolipoamide succinyltransferase (E2) component of the human alpha-ketoglutarate dehydrogenase complex (hKGDHc) revealed by cryo-EM and cross-linking mass spectrometry: Implications for the overall hKGDHc structure.,Nagy B, Polak M, Ozohanics O, Zambo Z, Szabo E, Hubert A, Jordan F, Novacek J, Adam-Vizi V, Ambrus A Biochim Biophys Acta Gen Subj. 2021 Mar 5;1865(6):129889. doi:, 10.1016/j.bbagen.2021.129889. PMID:33684457[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang Y, Guo YR, Liu K, Yin Z, Liu R, Xia Y, Tan L, Yang P, Lee JH, Li XJ, Hawke D, Zheng Y, Qian X, Lyu J, He J, Xing D, Tao YJ, Lu Z. KAT2A coupled with the alpha-KGDH complex acts as a histone H3 succinyltransferase. Nature. 2017 Dec 14;552(7684):273-277. doi: 10.1038/nature25003. Epub 2017 Dec 6. PMID:29211711 doi:http://dx.doi.org/10.1038/nature25003
- ↑ Nagy B, Polak M, Ozohanics O, Zambo Z, Szabo E, Hubert A, Jordan F, Novacek J, Adam-Vizi V, Ambrus A. Structure of the dihydrolipoamide succinyltransferase (E2) component of the human alpha-ketoglutarate dehydrogenase complex (hKGDHc) revealed by cryo-EM and cross-linking mass spectrometry: Implications for the overall hKGDHc structure. Biochim Biophys Acta Gen Subj. 2021 Mar 5;1865(6):129889. doi:, 10.1016/j.bbagen.2021.129889. PMID:33684457 doi:http://dx.doi.org/10.1016/j.bbagen.2021.129889
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