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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 85666122   9 TNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSQylHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFGN 81
Cdd:cd01663   1 TNHKDIGTLYLIFGLWSGLVGTSLSLLIRLELSQPGSQ--LGNDQLYNVIVTAHALIMIFFMVMPALIGGFGN 71

LAGLIDADG endonuclease;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85666122   245 LAGMTDADGNFSINLMNGKNRSSrampyYCLELRQNYQKNSnnnninfSYFYIMSAIATYFNVNLYSRERNLNllvstnn 324
Cdd:pfam00961   1 LAGFIDGDGSFSINVTKSKSYKG-----YRVRLRFQISLHS-------KDENLLEKIKNYLGIGSISKRKNDN------- 61

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 85666122   325 tyktYYSYKVmVANTYKNIKVMEYFNKYSLLSSKHLDFLDWSK 367
Cdd:pfam00961  62 ----TVIYII-SNSKKSLNIIIPYFDKYPLLTSKYLDYLDFKK 99

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 85666122   9 TNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSQylHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFGN 81
Cdd:cd01663   1 TNHKDIGTLYLIFGLWSGLVGTSLSLLIRLELSQPGSQ--LGNDQLYNVIVTAHALIMIFFMVMPALIGGFGN 71

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85666122   2 VQRWLYSTNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSQYLhgNSQLFNVLVVGHAVLMIFFLVMPaLIGGFGN 81
Cdd:COG0843   6 WRRWLTTVDHKRIGIMYLVTAFVFLLIGGLLALLMRLQLAGPGLGLL--SPETYNQLFTMHGTIMIFFFATP-FLAGFGN 82

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 85666122    13 DIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSQYLhgNSQLFNVLVVGHAVLMIFFLVMPAlIGGFGN 81
Cdd:pfam00115   1 RIGLLYLVTALVWFLVGGLLGLLIRLQLAFPGLNFL--SPLTYNQLRTLHGNLMIFWFATPF-LFGFGN 66

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 85666122   9 TNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSQylHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFGN 81
Cdd:cd01663   1 TNHKDIGTLYLIFGLWSGLVGTSLSLLIRLELSQPGSQ--LGNDQLYNVIVTAHALIMIFFMVMPALIGGFGN 71

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85666122    1 MVQRWLYSTNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSqyLHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFG 80
Cdd:MTH00167   2 WINRWLFSTNHKDIGTLYFIFGAWAGMVGTALSLLIRAELSQPGS--LLGDDQIYNVIVTAHAFVMIFFMVMPIMIGGFG 79

                 .
gi 85666122   81 N 81
Cdd:MTH00167  80 N 80

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85666122    2 VQRWLYSTNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSqyLHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFGN 81
Cdd:MTH00142   1 MMRWLFSTNHKDIGTLYFLFGAWAGMVGTGLSLLIRAELGQPGS--LLGDDQLYNVIVTAHAFVMIFFMVMPVMIGGFGN 78

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 85666122    4 RWLYSTNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSqyLHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFGN 81
Cdd:MTH00184   7 RWLFSTNHKDIGTLYLLFGAFAGMIGTAFSMLIRLELSAPGS--MLGDDHLYNVIVTAHAFVMIFFLVMPVMIGGFGN 82

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85666122    2 VQRWLYSTNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSqyLHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFGN 81
Cdd:MTH00037   3 LSRWLFSTNHKDIGTLYLIFGAWAGMVGTAMSVIIRTELAQPGS--LLQDDQIYNVIVTAHALVMIFFMVMPIMIGGFGN 80

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 85666122    4 RWLYSTNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSqyLHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFGN 81
Cdd:MTH00182   7 RWVFSTNHKDIGTLYLVFGAGAGMIGTAFSMLIRLELSAPGA--MLGDDHLYNVIVTAHAFIMIFFLVMPVMIGGFGN 82

cytochrome c oxidase subunit I; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85666122    1 MVQRWLYSTNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSqyLHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFG 80
Cdd:MTH00103   2 FINRWLFSTNHKDIGTLYLLFGAWAGMVGTALSLLIRAELGQPGT--LLGDDQIYNVIVTAHAFVMIFFMVMPIMIGGFG 79

                 .
gi 85666122   81 N 81
Cdd:MTH00103  80 N 80

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 85666122    4 RWLYSTNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSqyLHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFGN 81
Cdd:MTH00026   6 RWFFSCNHKDIGSLYLVFGALSGAIGTAFSMLIRLELSSPGS--MLGDDHLYNVIVTAHAFVMIFFLVMPTMIGGFGN 81

cytochrome c oxidase subunit I; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 85666122    5 WLYSTNAKDIAVLYFMLAIFSGMAGTAMSLIIRLELAAPgsQYLHGNSQLFNVLVVGHAVLMIFFLVMPALIGGFGN 81
Cdd:MTH00048   7 WLFTLDHKRIGVIYTLLGVWSGFVGLSLSLLIRLNFLDP--YYNVISLDVYNFLITNHGIIMIFFFLMPVLIGGFGN 81

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 85666122    13 DIAVLYFMLAIFSGMAGTAMSLIIRLELAAPGSQYLhgNSQLFNVLVVGHAVLMIFFLVMPAlIGGFGN 81
Cdd:pfam00115   1 RIGLLYLVTALVWFLVGGLLGLLIRLQLAFPGLNFL--SPLTYNQLRTLHGNLMIFWFATPF-LFGFGN 66

LAGLIDADG endonuclease;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 85666122   245 LAGMTDADGNFSINLMNGKNRSSrampyYCLELRQNYQKNSnnnninfSYFYIMSAIATYFNVNLYSRERNLNllvstnn 324
Cdd:pfam00961   1 LAGFIDGDGSFSINVTKSKSYKG-----YRVRLRFQISLHS-------KDENLLEKIKNYLGIGSISKRKNDN------- 61

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 85666122   325 tyktYYSYKVmVANTYKNIKVMEYFNKYSLLSSKHLDFLDWSK 367
Cdd:pfam00961  62 ----TVIYII-SNSKKSLNIIIPYFDKYPLLTSKYLDYLDFKK 99