5z62

Structural highlights

Disease

[COX7B_HUMAN] Microphthalmia with linear skin defects syndrome. The disease is caused by mutations affecting the gene represented in this entry. [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. [CX6A1_HUMAN] Autosomal recessive intermediate Charcot-Marie-Tooth disease type D. The disease is caused by mutations affecting the gene represented in this entry. [COX2_HUMAN] Isolated cytochrome C oxidase deficiency;MELAS. The disease is caused by mutations affecting the gene represented in this entry. [NDUA4_HUMAN] Leigh syndrome with leukodystrophy. The disease is caused by mutations affecting the gene represented in this entry. [CX6B1_HUMAN] Isolated cytochrome C oxidase deficiency. The disease is caused by mutations affecting the gene represented in this entry. [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. [COX8A_HUMAN] Isolated cytochrome C oxidase deficiency. [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.^[3]

Function

[COX5B_HUMAN] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [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.^[4] [COX3_HUMAN] Subunits I, II and III form the functional core of the enzyme complex. [CX6A1_HUMAN] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [COX6C_HUMAN] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [COX7C_HUMAN] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [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. [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.^[5] [CX6B1_HUMAN] Connects the two COX monomers into the physiological dimeric form. [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. [COX41_HUMAN] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [COX8A_HUMAN] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [CX7A2_HUMAN] This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport. [COX5A_HUMAN] This is the heme A-containing chain of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.

References

1. ↑ 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
2. ↑ 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
3. ↑ Baertling F, Al-Murshedi F, Sanchez-Caballero L, Al-Senaidi K, Joshi NP, Venselaar H, van den Brand MA, Nijtmans LG, Rodenburg RJ. Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive. Hum Mutat. 2017 Jun;38(6):692-703. doi: 10.1002/humu.23210. Epub 2017 Mar 23. PMID:28247525 doi:http://dx.doi.org/10.1002/humu.23210
4. ↑ Indrieri A, van Rahden VA, Tiranti V, Morleo M, Iaconis D, Tammaro R, D'Amato I, Conte I, Maystadt I, Demuth S, Zvulunov A, Kutsche K, Zeviani M, Franco B. Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease. Am J Hum Genet. 2012 Nov 2;91(5):942-9. doi: 10.1016/j.ajhg.2012.09.016. PMID:23122588 doi:http://dx.doi.org/10.1016/j.ajhg.2012.09.016
5. ↑ Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E, Landazuri MO, Enriquez JA. NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. Cell Metab. 2012 Sep 5;16(3):378-86. doi: 10.1016/j.cmet.2012.07.015. Epub 2012, Aug 16. PMID:22902835 doi:http://dx.doi.org/10.1016/j.cmet.2012.07.015
6. ↑ 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