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| | <SX load='5z62' size='340' side='right' viewer='molstar' caption='[[5z62]], [[Resolution|resolution]] 3.60Å' scene=''> | | <SX load='5z62' size='340' side='right' viewer='molstar' caption='[[5z62]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5z62]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z62 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z62 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5z62]] is a 10 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=5Z62 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z62 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=HEA:HEME-A'>HEA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 3.6Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cytochrome-c_oxidase Cytochrome-c oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.9.3.1 1.9.3.1] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=HEA:HEME-A'>HEA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5z62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z62 OCA], [http://pdbe.org/5z62 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z62 RCSB], [http://www.ebi.ac.uk/pdbsum/5z62 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z62 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=5z62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z62 OCA], [https://pdbe.org/5z62 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z62 RCSB], [https://www.ebi.ac.uk/pdbsum/5z62 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z62 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/COX7B_HUMAN COX7B_HUMAN]] Microphthalmia with linear skin defects syndrome. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/COX3_HUMAN COX3_HUMAN]] MELAS;Isolated cytochrome C oxidase deficiency;Genetic recurrent myoglobinuria;Leber hereditary optic neuropathy. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis. [[http://www.uniprot.org/uniprot/CX6A1_HUMAN CX6A1_HUMAN]] Autosomal recessive intermediate Charcot-Marie-Tooth disease type D. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/COX2_HUMAN COX2_HUMAN]] Isolated cytochrome C oxidase deficiency;MELAS. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/NDUA4_HUMAN NDUA4_HUMAN]] Leigh syndrome with leukodystrophy. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/CX6B1_HUMAN CX6B1_HUMAN]] Isolated cytochrome C oxidase deficiency. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/COX1_HUMAN COX1_HUMAN]] Mitochondrial non-syndromic sensorineural deafness with susceptibility to aminoglycoside exposure;Mitochondrial non-syndromic sensorineural deafness;Genetic recurrent myoglobinuria;Isolated cytochrome C oxidase deficiency;Leber hereditary optic neuropathy;MELAS. The disease is caused by mutations affecting the gene represented in this entry. MT-CO1 may play a role in the pathogenesis of acquired idiopathic sideroblastic anemia, a disease characterized by inadequate formation of heme and excessive accumulation of iron in mitochondria. Mitochondrial iron overload may be attributable to mutations of mitochondrial DNA because these can cause respiratory chain dysfunction, thereby impairing reduction of ferric iron to ferrous iron. The reduced form of iron is essential to the last step of mitochondrial heme biosynthesis.<ref>PMID:9389715</ref> <ref>PMID:9851701</ref> The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis. [[http://www.uniprot.org/uniprot/COX8A_HUMAN COX8A_HUMAN]] Isolated cytochrome C oxidase deficiency. [[http://www.uniprot.org/uniprot/COX5A_HUMAN COX5A_HUMAN]] Isolated cytochrome C oxidase deficiency. Mitochondrial complex IV deficiency is a rare condition caused by mutation in COX5A that lead to pulmonary arterial hypertension (PAH), failure to thrive and lactic acidemia.<ref>PMID:28247525</ref> | + | [https://www.uniprot.org/uniprot/COX1_HUMAN COX1_HUMAN] Mitochondrial non-syndromic sensorineural deafness with susceptibility to aminoglycoside exposure;Mitochondrial non-syndromic sensorineural deafness;Genetic recurrent myoglobinuria;Isolated cytochrome C oxidase deficiency;Leber hereditary optic neuropathy;MELAS. The disease is caused by mutations affecting the gene represented in this entry. MT-CO1 may play a role in the pathogenesis of acquired idiopathic sideroblastic anemia, a disease characterized by inadequate formation of heme and excessive accumulation of iron in mitochondria. Mitochondrial iron overload may be attributable to mutations of mitochondrial DNA because these can cause respiratory chain dysfunction, thereby impairing reduction of ferric iron to ferrous iron. The reduced form of iron is essential to the last step of mitochondrial heme biosynthesis.<ref>PMID:9389715</ref> <ref>PMID:9851701</ref> The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/COX5B_HUMAN COX5B_HUMAN]] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [[http://www.uniprot.org/uniprot/COX7B_HUMAN COX7B_HUMAN]] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. Plays a role in proper central nervous system (CNS) development in vertebrates.<ref>PMID:23122588</ref> [[http://www.uniprot.org/uniprot/COX3_HUMAN COX3_HUMAN]] Subunits I, II and III form the functional core of the enzyme complex. [[http://www.uniprot.org/uniprot/CX6A1_HUMAN CX6A1_HUMAN]] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [[http://www.uniprot.org/uniprot/COX6C_HUMAN COX6C_HUMAN]] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [[http://www.uniprot.org/uniprot/COX2_HUMAN COX2_HUMAN]] Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Subunit 2 transfers the electrons from cytochrome c via its binuclear copper A center to the bimetallic center of the catalytic subunit 1. [[http://www.uniprot.org/uniprot/COX7C_HUMAN COX7C_HUMAN]] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [[http://www.uniprot.org/uniprot/NDUA4_HUMAN NDUA4_HUMAN]] Cytochrome c oxidase (COX, complex IV) is the terminal component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water. Required for complex IV maintenance.<ref>PMID:22902835</ref> [[http://www.uniprot.org/uniprot/CX6B1_HUMAN CX6B1_HUMAN]] Connects the two COX monomers into the physiological dimeric form. [[http://www.uniprot.org/uniprot/COX1_HUMAN COX1_HUMAN]] Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. CO I is the catalytic subunit of the enzyme. Electrons originating in cytochrome c are transferred via the copper A center of subunit 2 and heme A of subunit 1 to the bimetallic center formed by heme A3 and copper B. [[http://www.uniprot.org/uniprot/COX41_HUMAN COX41_HUMAN]] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [[http://www.uniprot.org/uniprot/CX7A2_HUMAN CX7A2_HUMAN]] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [[http://www.uniprot.org/uniprot/COX8A_HUMAN COX8A_HUMAN]] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [[http://www.uniprot.org/uniprot/COX5A_HUMAN COX5A_HUMAN]] This is the heme A-containing chain of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. | + | [https://www.uniprot.org/uniprot/COX1_HUMAN COX1_HUMAN] Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. CO I is the catalytic subunit of the enzyme. Electrons originating in cytochrome c are transferred via the copper A center of subunit 2 and heme A of subunit 1 to the bimetallic center formed by heme A3 and copper B. |
| | <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: Cytochrome-c oxidase]] | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gu, J]] | + | [[Category: Gu J]] |
| - | [[Category: Wu, M]] | + | [[Category: Wu M]] |
| - | [[Category: Yang, M]] | + | [[Category: Yang M]] |
| - | [[Category: Zong, S]] | + | [[Category: Zong S]] |
| - | [[Category: Cytochrome c oxidase]]
| + | |
| - | [[Category: Electron transport]]
| + | |
| Structural highlights
Disease
COX1_HUMAN Mitochondrial non-syndromic sensorineural deafness with susceptibility to aminoglycoside exposure;Mitochondrial non-syndromic sensorineural deafness;Genetic recurrent myoglobinuria;Isolated cytochrome C oxidase deficiency;Leber hereditary optic neuropathy;MELAS. The disease is caused by mutations affecting the gene represented in this entry. MT-CO1 may play a role in the pathogenesis of acquired idiopathic sideroblastic anemia, a disease characterized by inadequate formation of heme and excessive accumulation of iron in mitochondria. Mitochondrial iron overload may be attributable to mutations of mitochondrial DNA because these can cause respiratory chain dysfunction, thereby impairing reduction of ferric iron to ferrous iron. The reduced form of iron is essential to the last step of mitochondrial heme biosynthesis.[1] [2] The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may be involved in disease pathogenesis.
Function
COX1_HUMAN Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. CO I is the catalytic subunit of the enzyme. Electrons originating in cytochrome c are transferred via the copper A center of subunit 2 and heme A of subunit 1 to the bimetallic center formed by heme A3 and copper B.
Publication Abstract from PubMed
Respiration is one of the most basic features of living organisms, and the electron transport chain complexes are probably the most complicated protein system in mitochondria. Complex-IV is the terminal enzyme of the electron transport chain, existing either as randomly scattered complexes or as a component of supercomplexes. NDUFA4 was previously assumed as a subunit of complex-I, but recent biochemical data suggested it may be a subunit of complex-IV. However, no structural evidence supporting this notion was available till now. Here we obtained the 3.3 A resolution structure of complex-IV derived from the human supercomplex I1III2IV1 and assigned the NDUFA4 subunit into complex-IV. Intriguingly, NDUFA4 lies exactly at the dimeric interface observed in previously reported crystal structures of complex-IV homodimer which would preclude complex-IV dimerization. Combining previous structural and biochemical data shown by us and other groups, we propose that the intact complex-IV is a monomer containing 14 subunits.
Structure of the intact 14-subunit human cytochrome c oxidase.,Zong S, Wu M, Gu J, Liu T, Guo R, Yang M Cell Res. 2018 Oct;28(10):1026-1034. doi: 10.1038/s41422-018-0071-1. Epub 2018, Jul 20. PMID:30030519[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gattermann N, Retzlaff S, Wang YL, Hofhaus G, Heinisch J, Aul C, Schneider W. Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia. Blood. 1997 Dec 15;90(12):4961-72. PMID:9389715
- ↑ Broker S, Meunier B, Rich P, Gattermann N, Hofhaus G. MtDNA mutations associated with sideroblastic anaemia cause a defect of mitochondrial cytochrome c oxidase. Eur J Biochem. 1998 Nov 15;258(1):132-8. PMID:9851701
- ↑ Zong S, Wu M, Gu J, Liu T, Guo R, Yang M. Structure of the intact 14-subunit human cytochrome c oxidase. Cell Res. 2018 Oct;28(10):1026-1034. doi: 10.1038/s41422-018-0071-1. Epub 2018, Jul 20. PMID:30030519 doi:http://dx.doi.org/10.1038/s41422-018-0071-1
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