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 554520901   1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPVMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:cd01663   20 VGTSLSLLIRLELSQPGSQLGNDQLYNVIVTAHALIMIFFMVMPALIGGFGNWLVPLMIGAPDMAFPRLNNLSFWLLPPS 99

                         90
                 ....*....|....*.
gi 554520901  81 LFLLILSSFINTGVGT 96
Cdd:cd01663  100 LLLLLLSALVEGGAGT 115

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 554520901    1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPvMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:pfam00115  16 VGGLLGLLIRLQLAFPGLNFLSPLTYNQLRTLHGNLMIFWFATP-FLFGFGNYLVPLMIGARDMAFPRLNALSFWLVVLG 94

                  ....*..
gi 554520901   81 LFLLILS 87
Cdd:pfam00115  95 AVLLLAS 101

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 554520901   1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPVMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:cd01663   20 VGTSLSLLIRLELSQPGSQLGNDQLYNVIVTAHALIMIFFMVMPALIGGFGNWLVPLMIGAPDMAFPRLNNLSFWLLPPS 99

                         90
                 ....*....|....*.
gi 554520901  81 LFLLILSSFINTGVGT 96
Cdd:cd01663  100 LLLLLLSALVEGGAGT 115

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 554520901   1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPVMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:MTH00116  29 VGTALSLLIRAELGQPGTLLGDDQIYNVIVTAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPS 108

                         90
                 ....*....|....*.
gi 554520901  81 LFLLILSSFINTGVGT 96
Cdd:MTH00116 109 FLLLLASSTVEAGAGT 124

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 554520901   1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPVMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:MTH00142  27 VGTGLSLLIRAELGQPGSLLGDDQLYNVIVTAHAFVMIFFMVMPVMIGGFGNWLVPLMLGAPDMAFPRMNNMSFWLLPPA 106

                         90
                 ....*....|....*.
gi 554520901  81 LFLLILSSFINTGVGT 96
Cdd:MTH00142 107 LLLLLSSAAVESGAGT 122

cytochrome c oxidase subunit I; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 554520901   1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPVMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:MTH00007  26 LGTSMSLLIRIELGQPGAFLGSDQLYNTIVTAHAFLMIFFLVMPVFIGGFGNWLVPLMLGAPDMAFPRLNNMSFWLLPPA 105

                         90
                 ....*....|....*.
gi 554520901  81 LFLLILSSFINTGVGT 96
Cdd:MTH00007 106 LILLVSSAAVEKGVGT 121

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 554520901   1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPVMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:MTH00037  29 VGTAMSVIIRTELAQPGSLLQDDQIYNVIVTAHALVMIFFMVMPIMIGGFGNWLIPLMIGAPDMAFPRMNNMSFWLIPPS 108

                         90
                 ....*....|....*.
gi 554520901  81 LFLLILSSFINTGVGT 96
Cdd:MTH00037 109 FLLLLASAGVESGAGT 124

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 554520901   1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPVMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:MTH00182  31 IGTAFSMLIRLELSAPGAMLGDDHLYNVIVTAHAFIMIFFLVMPVMIGGFGNWLVPLYIGAPDMAFPRLNNISFWLLPPA 110

                         90
                 ....*....|....*.
gi 554520901  81 LFLLILSSFINTGVGT 96
Cdd:MTH00182 111 LILLLGSAFVEQGAGT 126

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 554520901   1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPVMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:MTH00079  30 VGTSLSLIIRLELSKPGLLLGNGQLYNSVITAHAILMIFFMVMPSMIGGFGNWMLPLMLGAPDMSFPRLNNLSFWLLPTS 109

                         90
                 ....*....|....*.
gi 554520901  81 LFLLILSSFINTGVGT 96
Cdd:MTH00079 110 LFLILDSCFVDMGPGT 125

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 554520901   1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPVMIGGFGNWLIPlMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:cd00919   18 LGGLLALLIRLELATPGSLFLDPQLYNQLVTAHGVIMIFFFVMPAIFGGFGNLLPP-LIGARDLAFPRLNNLSFWLFPPG 96

                         90
                 ....*....|....*.
gi 554520901  81 LFLLILSSFINTGVGT 96
Cdd:cd00919   97 LLLLLSSVLVGGGAGT 112

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 554520901   1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPvMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:COG0843   32 IGGLLALLMRLQLAGPGLGLLSPETYNQLFTMHGTIMIFFFATP-FLAGFGNYLVPLQIGARDMAFPRLNALSFWLYLFG 110

                         90
                 ....*....|....*.
gi 554520901  81 LFLLILSSFINTGVGT 96
Cdd:COG0843  111 GLLLLISLFVGGAADV 126

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 554520901    1 LGFSMSMIIRLELGMPGSLIKNDQIYNSIVTSHAFIMIFFMVMPvMIGGFGNWLIPLMLGAPDMSFPRMNNMSFWLLIPS 80
Cdd:pfam00115  16 VGGLLGLLIRLQLAFPGLNFLSPLTYNQLRTLHGNLMIFWFATP-FLFGFGNYLVPLMIGARDMAFPRLNALSFWLVVLG 94

                  ....*..
gi 554520901   81 LFLLILS 87
Cdd:pfam00115  95 AVLLLAS 101