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 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:cd01663    24 LSLLIRLELSQPGSQLGNDQLYNVIVTAHALIMIFFMVMPALIGGFGNWLVPLMIGAPDMAFPRLNNLSFWLLPPSLLLL 103

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2056530233  81 LSSSMTDGGAGTGWTVYPPLAGAIAHSGTSVDLAI 115
Cdd:cd01663   104 LLSALVEGGAGTGWTVYPPLSSILAHSGPSVDLAI 138

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 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPiMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:pfam00115  20 LGLLIRLQLAFPGLNFLSPLTYNQLRTLHGNLMIFWFATP-FLFGFGNYLVPLMIGARDMAFPRLNALSFWLVVLGAVLL 98

                          90       100
                  ....*....|....*....|..
gi 2056530233  81 LSSSmtdGGAGTGWTVYPPLAG 102
Cdd:pfam00115  99 LASF---GGATTGWTEYPPLVG 117

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 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:cd01663    24 LSLLIRLELSQPGSQLGNDQLYNVIVTAHALIMIFFMVMPALIGGFGNWLVPLMIGAPDMAFPRLNNLSFWLLPPSLLLL 103

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2056530233  81 LSSSMTDGGAGTGWTVYPPLAGAIAHSGTSVDLAI 115
Cdd:cd01663   104 LLSALVEGGAGTGWTVYPPLSSILAHSGPSVDLAI 138

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:MTH00116   33 LSLLIRAELGQPGTLLGDDQIYNVIVTAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSFLLL 112

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2056530233  81 LSSSMTDGGAGTGWTVYPPLAGAIAHSGTSVDLAI 115
Cdd:MTH00116  113 LASSTVEAGAGTGWTVYPPLAGNLAHAGASVDLAI 147

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:MTH00223   30 LSLLIRAELGQPGALLGDDQLYNVIVTAHAFVMIFFLVMPMMIGGFGNWLVPLMLGAPDMAFPRLNNMSFWLLPPSLYLL 109

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2056530233  81 LSSSMTDGGAGTGWTVYPPLAGAIAHSGTSVDLAI 115
Cdd:MTH00223  110 LSSSAVESGVGTGWTVYPPLSSNLAHAGPSVDLAI 144

cytochrome c oxidase subunit I; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:MTH00103   33 LSLLIRAELGQPGTLLGDDQIYNVIVTAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSFLLL 112

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2056530233  81 LSSSMTDGGAGTGWTVYPPLAGAIAHSGTSVDLAI 115
Cdd:MTH00103  113 LASSMVEAGAGTGWTVYPPLAGNLAHAGASVDLTI 147

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:MTH00037   33 MSVIIRTELAQPGSLLQDDQIYNVIVTAHALVMIFFMVMPIMIGGFGNWLIPLMIGAPDMAFPRMNNMSFWLIPPSFLLL 112

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2056530233  81 LSSSMTDGGAGTGWTVYPPLAGAIAHSGTSVDLAI 115
Cdd:MTH00037  113 LASAGVESGAGTGWTIYPPLSSNIAHAGGSVDLAI 147

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:MTH00182   35 FSMLIRLELSAPGAMLGDDHLYNVIVTAHAFIMIFFLVMPVMIGGFGNWLVPLYIGAPDMAFPRLNNISFWLLPPALILL 114

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2056530233  81 LSSSMTDGGAGTGWTVYPPLAGAIAHSGTSVDLAI 115
Cdd:MTH00182  115 LGSAFVEQGAGTGWTVYPPLSSIQAHSGGAVDMAI 149

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:MTH00079   34 LSLIIRLELSKPGLLLGNGQLYNSVITAHAILMIFFMVMPSMIGGFGNWMLPLMLGAPDMSFPRLNNLSFWLLPTSLFLI 113

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2056530233  81 LSSSMTDGGAGTGWTVYPPLAgAIAHSGTSVDLAI 115
Cdd:MTH00079  114 LDSCFVDMGPGTSWTVYPPLS-TLGHPGSSVDLAI 147

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 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPIMIGGFGNWLVPlMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:cd00919    22 LALLIRLELATPGSLFLDPQLYNQLVTAHGVIMIFFFVMPAIFGGFGNLLPP-LIGARDLAFPRLNNLSFWLFPPGLLLL 100

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2056530233  81 LSSSMTDGGAGTGWTVYPPLAGAIAHSGTSVDLAI 115
Cdd:cd00919   101 LSSVLVGGGAGTGWTFYPPLSTLSYSSGVGVDLAI 135

Ubiquinol oxidase subunit I. Ubiquinol oxidase, the terminal oxidase in the respiratory chains of aerobic bacteria, is a multi-chain transmembrane protein located in the cell membrane. It catalyzes the reduction of O2 and simultaneously pumps protons across the membrane. The number of subunits in ubiquinol oxidase varies from two to five. Subunit I 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 from ubiquinol 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 ubiquinol 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. It is generally believed that the channels contain water molecules that act as 'proton wires' to transfer the protons. A well-defined pathway for the transfer of pumped protons beyond the binuclear center has not been identified. Electrons are believed to be transferred directly from ubiquinol (the electron donor) to the low-spin heme, and directly from the low-spin heme to the binuclear center.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPIMIGgFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:cd01662    28 DALLMRTQLALPGNDFLSPEHYNQIFTMHGTIMIFLFAMPLVFG-LMNYLVPLQIGARDVAFPRLNALSFWLFLFGGLLL 106

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2056530233  81 LSSSMTDGGAGTGWTVYPPLAGAIAHSGTSVDLAI 115
Cdd:cd01662   107 NASLLIGGFPDAGWFAYPPLSGLEYSPGVGVDYWI 141

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 2056530233   1 MSMIIRIELGQPGTMIGDDQIYNVIITAHAFVMIFFMVMPiMIGGFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLL 80
Cdd:pfam00115  20 LGLLIRLQLAFPGLNFLSPLTYNQLRTLHGNLMIFWFATP-FLFGFGNYLVPLMIGARDMAFPRLNALSFWLVVLGAVLL 98

                          90       100
                  ....*....|....*....|..
gi 2056530233  81 LSSSmtdGGAGTGWTVYPPLAG 102
Cdd:pfam00115  99 LASF---GGATTGWTEYPPLVG 117

cytochrome o ubiquinol oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2056530233  22 YNVIITAHAFVMIFFMVMPIMIGgFGNWLVPLMIGAPDMAFPRMNNMSFWLLPPSLMLLLSSSMTDGGAGTGWTVYPPLA 101
Cdd:PRK15017   99 YDQIFTAHGVIMIFFVAMPFVIG-LMNLVVPLQIGARDVAFPFLNNLSFWFTVVGVILVNVSLGVGEFAQTGWLAYPPLS 177

                          90
                  ....*....|....
gi 2056530233 102 GAIAHSGTSVDLAI 115
Cdd:PRK15017  178 GIEYSPGVGVDYWI 191