Cytochrome C oxidase subunit I. Cytochrome c oxidase (CcO), the terminal oxidase in the respiratory chains of eukaryotes and most bacteria, is a multi-chain transmembrane protein located in the inner membrane of mitochondria and the cell membrane of prokaryotes. It catalyzes the reduction of O2 and simultaneously pumps protons across the membrane. The number of subunits varies from three to five in bacteria and up to 13 in mammalian mitochondria. Only subunits I and II are essential for function, but subunit III, which is also conserved, may play a role in assembly or oxygen delivery to the active site. Subunits I, II, and III of mammalian CcO are encoded within the mitochondrial genome and the remaining 10 subunits are encoded within the nuclear genome. Subunit I contains a heme-copper binuclear center (the active site where O2 is reduced to water) formed by a high-spin heme (heme a3) and a copper ion (CuB). It also contains a low-spin heme (heme a), believed to participate in the transfer of electrons to the binuclear center. For every reduction of an O2 molecule, eight protons are taken from the inside aqueous compartment and four electrons are taken from cytochrome c on the opposite side of the membrane. The four electrons and four of the protons are used in the reduction of O2; the four remaining protons are pumped across the membrane. This charge separation of four charges contributes to the electrochemical gradient used for ATP synthesis. Two proton channels, the D-pathway and K-pathway, leading to the binuclear center have been identified in subunit I. A well-defined pathway for the transfer of pumped protons beyond the binuclear center has not been identified. Electrons are transferred from cytochrome c (the electron donor) to heme a via the CuA binuclear site in subunit II, and directly from heme a to the binuclear center.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 75811810   1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTTWNMGSSMGSFISLTAVLIMIFIIWEALASKREVVSIP-YSSTN 79
Cdd:cd01663 404 HFWLMFIGVNLTFFPQHFLGLAGMPRRYPDYPDAYAGWNMISSIGSLISFVSVLLFLFIVWESFVSGRKVIFNVgEGSTS 483

                ....*
gi 75811810  80 LEWLH 84
Cdd:cd01663 484 LEWTL 488

Cytochrome C and Quinol oxidase polypeptide I; Cytochrome c oxidase (E.C:7.1.1.9) is a key enzyme in aerobic metabolism. Proton pumping haem-copper oxidases represent the terminal, energy-transfer enzymes of respiratory chains in prokaryotes and eukaryotes. The CuB-haem a3 (or haem o) binuclear centre, associated with the largest subunit I of cytochrome c and ubiquinol oxidases (E.C:1.10.3.11), is directly involved in the coupling between dioxygen reduction and proton pumping. Some terminal oxidases generate a transmembrane proton gradient across the plasma membrane (prokaryotes) or the mitochondrial inner membrane (eukaryotes). The enzyme complex consists of 3-4 subunits (prokaryotes) up to 13 polypeptides (mammals) of which only the catalytic subunit (equivalent to mammalian subunit I (COXI) is found in all haem-copper respiratory oxidases. The presence of a bimetallic centre (formed by a high-spin haem and copper B) as well as a low-spin haem, both ligated to six conserved histidine residues near the outer side of four transmembrane spans within CO I is common to all family members.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 75811810     1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYS----DYPDAYTTWNMGSSMGSFI 48
Cdd:pfam00115 381 HFWLLFIGFNLTFFPMHILGLLGMPRRYAppfiETVPAFQPLNWIRTIGGVL 432

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 75811810    1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTTWNMGSSMGSFISLTAVLIMIFIIWEALASKREVVSIPYSSTNL 80
Cdd:MTH00116 413 QFGVMFTGVNLTFFPQHFLGLAGMPRRYSDYPDAYTLWNTISSIGSLISMTAVIMLMFIIWEAFSSKRKVLQPELTTTNI 492

                         90
                 ....*....|....*....
gi 75811810   81 EWLHGCPPPYHTFEEPAFV 99
Cdd:MTH00116 493 EWIHGCPPPYHTFEEPAFV 511

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 75811810    1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTTWNMGSSMGSFISLTAVLIMIFIIWEALASKREVVSIPYSSTNL 80
Cdd:MTH00153 411 QFFIMFIGVNLTFFPQHFLGLAGMPRRYSDYPDAYTSWNVISSIGSTISLISILFFIFIIWESMISKRPVLFSLNLSSSI 490

                         90
                 ....*....|....*
gi 75811810   81 EWLHGCPPPYHTFEE 95
Cdd:MTH00153 491 EWLQNLPPAEHSYSE 505

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 75811810    1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTTWNMGSSMGSFISLTAVLIMIFIIWEALASKREVVSIPYSSTNL 80
Cdd:MTH00077 413 HFGVMFIGVNLTFFPQHFLGLAGMPRRYSDYPDAYTLWNTVSSIGSLISLVAVIMMMFIIWEAFSSKREVLTTELTSTNI 492

                         90       100
                 ....*....|....*....|.
gi 75811810   81 EWLHGCPPPYHTFEEPAFVKV 101
Cdd:MTH00077 493 EWLHGCPPPYHTFEEPSFVQT 513

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 75811810    1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTTWNMGSSMGSFISLTAVLIMIFIIWEALASKREVVSIPYSSTNL 80
Cdd:MTH00223 410 HFFLMFLGVNLTFFPQHFLGLAGMPRRYSDYPDCYTKWNQVSSFGSMISFVSVLFFMFIVWEAFVSQRSVVWSGHLSTSL 489

                         90
                 ....*....|....*....
gi 75811810   81 EWLHGCPPPYHTFEEPAFV 99
Cdd:MTH00223 490 EWDNLLPADFHNNSETGAL 508

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 75811810    1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTTWNMGSSMGSFISLTAVLIMIFIIWEALASKREVVSIPYSSTNL 80
Cdd:MTH00037 413 HFFLMFIGVNLTFFPQHFLGLAGMPRRYSDYPDAYTLWNTVSSIGSTISLVATLFFLFLIWEAFASQREVISPEFSSSSL 492

                         90       100
                 ....*....|....*....|...
gi 75811810   81 EWLHGC-PPPYHTFEEPAFVKVI 102
Cdd:MTH00037 493 EWQYSSfPPSHHTFDETPSTVIL 515

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 75811810    1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTTWNMGSSMGSFISLTAVLIMIFIIWEALASKREVVS----IPYS 76
Cdd:MTH00182 415 HFWLMFIGVNLTFFPQHFLGLAGFPRRYSDFADAFAGWNLVSSLGSIISIVGVVWFIYIIYDAYVREEKFIGwkegTGES 494

                         90       100
                 ....*....|....*....|...
gi 75811810   77 STNLEWLHGCPPPYHTFEEPAFV 99
Cdd:MTH00182 495 WASLEWVHSSPPLFHTYNELPFV 517

Heme/copper-type cytochrome/quinol oxidase, subunit 1 [Energy production and conversion];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 75811810   1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYSDYP--DAYTTWNMGSSMGSFISLTAVLIMIFIIWEALASKREVVSIPYSST 78
Cdd:COG0843 414 HFWLWFIGFNLTFFPMHILGLLGMPRRYATYPpePGWQPLNLISTIGAFILAVGFLLFLINLVVSLRKGPKAGGNPWGAR 493

                        90
                ....*....|....*...
gi 75811810  79 NLEWLHGCPPPYHTFEEP 96
Cdd:COG0843 494 TLEWATPSPPPLYNFASI 511

Heme-copper oxidase subunit I. Heme-copper oxidases are transmembrane protein complexes in the respiratory chains of prokaryotes and mitochondria which catalyze the reduction of O2 and simultaneously pump protons across the membrane. The superfamily is diverse in terms of electron donors, subunit composition, and heme types. The number of subunits varies from three to five in bacteria and up to 13 in mammalian mitochondria. It has been proposed that Archaea acquired heme-copper oxidases through gene transfer from Gram-positive bacteria. Membership in the superfamily is defined by subunit I, which contains a heme-copper binuclear center (the active site where O2 is reduced to water) formed by a high-spin heme and a copper ion. It also contains a low-spin heme, believed to participate in the transfer of electrons to the binuclear center. Only subunit I is common to the entire superfamily. For every reduction of an O2 molecule, eight protons are taken from the inside aqueous compartment and four electrons are taken from the electron donor on the opposite side of the membrane. The four electrons and four of the protons are used in the reduction of O2; the four remaining protons are pumped across the membrane. This charge separation of four charges contributes to the electrochemical gradient used for ATP synthesis. Two proton channels, the D-pathway and K-pathway, leading to the binuclear center have been identified in subunit I of cytochrome c oxidase (CcO) and ubiquinol oxidase. A well-defined pathway for the transfer of pumped protons beyond the binuclear center has not been identified. Electron transfer occurs in two segments: from the electron donor to the low-spin heme, and from the low-spin heme to the binuclear center. The first segment can be a multi-step process and varies among the different families, while the second segment, a direct transfer, is consistent throughout the superfamily.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 75811810   1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTTWNMGSSMGSFISLTAVLIMIFIIWEAL 64
Cdd:cd00919 400 HFWLWFIGFNLTFFPMHFLGLLGMPRRYADYPDGFAPWNFISSVGAFILGLGLLLFLGNLFLSL 463

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 75811810    1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYSDYPDAYTTWNMGSSMGSFISLTAVLIMIFIIWEA----------LASKREV 70
Cdd:MTH00026 416 HFWLMFIGVNITFFPQHFLGLAGLPRRYADYPDNFEDFNQISSFGSIISIIAVIWFIVVIFDAyyreepfdinIMAKGPL 495

                         90       100       110
                 ....*....|....*....|....*....|..
gi 75811810   71 VSI---PYSSTNLEWLHGCPPPYHTFEEPAFV 99
Cdd:MTH00026 496 IPFscqPAHFDTLEWSLTSPPEHHTYNELPYI 527

Cytochrome C and Quinol oxidase polypeptide I; Cytochrome c oxidase (E.C:7.1.1.9) is a key enzyme in aerobic metabolism. Proton pumping haem-copper oxidases represent the terminal, energy-transfer enzymes of respiratory chains in prokaryotes and eukaryotes. The CuB-haem a3 (or haem o) binuclear centre, associated with the largest subunit I of cytochrome c and ubiquinol oxidases (E.C:1.10.3.11), is directly involved in the coupling between dioxygen reduction and proton pumping. Some terminal oxidases generate a transmembrane proton gradient across the plasma membrane (prokaryotes) or the mitochondrial inner membrane (eukaryotes). The enzyme complex consists of 3-4 subunits (prokaryotes) up to 13 polypeptides (mammals) of which only the catalytic subunit (equivalent to mammalian subunit I (COXI) is found in all haem-copper respiratory oxidases. The presence of a bimetallic centre (formed by a high-spin haem and copper B) as well as a low-spin haem, both ligated to six conserved histidine residues near the outer side of four transmembrane spans within CO I is common to all family members.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 75811810     1 HFTIMFVGVNMTFFPQHFLGLSGMPRRYS----DYPDAYTTWNMGSSMGSFI 48
Cdd:pfam00115 381 HFWLLFIGFNLTFFPMHILGLLGMPRRYAppfiETVPAFQPLNWIRTIGGVL 432

ba3-like heme-copper oxidase subunit I. The ba3 family of heme-copper oxidases are transmembrane protein complexes in the respiratory chains of prokaryotes and some archaea which catalyze the reduction of O2 and simultaneously pump protons across the membrane. It has been proposed that Archaea acquired heme-copper oxidases through gene transfer from Gram-positive bacteria. The ba3 family contains oxidases that lack the conserved residues that form the D- and K-pathways in CcO and ubiquinol oxidase. Instead they contain a potential alternative K-pathway. Additional proton channels have been proposed for this family of oxidases but none have been identified definitively. For general information on the heme-copper oxidase superfamily, please see cd00919.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 75811810   6 FVGVNMTFFPQHFLGLSGMPRR--YSDYPDAY-----TTWNMGSSMGSFISLTAVLIMIFII 60
Cdd:cd01660 407 FVGMTIMSTAMHVAGLLGAPRRtaEAQYGGLPaagewAPYQQLMAIGGTILFVSGALFLYIL 468