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 2205982155   1 LSVYTFH-GKSVDLSILALHLAGVGSLTGAINTVCSSTRLR-RDYRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLT 78
Cdd:cd01663   123 LSSILAHsGPSVDLAIFSLHLAGISSILGAINFITTIFNMRaPGMTLEKMPLFVWSVLITAFLLLLSLPVLAGAITMLLT 202

                          90       100
                  ....*....|....*....|....
gi 2205982155  79 DRHFNTSFFHPGGGGDPVLFQHLF 102
Cdd:cd01663   203 DRNFNTSFFDPAGGGDPILYQHLF 226

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 2205982155   1 LSVYTFH-GKSVDLSILALHLAGVGSLTGAINTVCSSTRLR-RDYRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLT 78
Cdd:cd01663   123 LSSILAHsGPSVDLAIFSLHLAGISSILGAINFITTIFNMRaPGMTLEKMPLFVWSVLITAFLLLLSLPVLAGAITMLLT 202

                          90       100
                  ....*....|....*....|....
gi 2205982155  79 DRHFNTSFFHPGGGGDPVLFQHLF 102
Cdd:cd01663   203 DRNFNTSFFDPAGGGDPILYQHLF 226

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2205982155   1 LSVYTFH-GKSVDLSILALHLAGVGSLTGAINTVCSSTRLRRDY-RMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLT 78
Cdd:COG0843   134 LSGLEASpGVGVDLWLLGLALFGVGSILGGVNFIVTILKMRAPGmTLMRMPLFTWAALVTSILILLAFPVLAAALLLLLL 213

                          90       100
                  ....*....|....*....|....
gi 2205982155  79 DRHFNTSFFHPGGGGDPVLFQHLF 102
Cdd:COG0843   214 DRSLGTHFFDPAGGGDPLLWQHLF 237

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 2205982155   1 LSVYTFH-GKSVDLSILALHLAGVGSLTGAINTVCSSTRLR-RDYRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLT 78
Cdd:cd01663   123 LSSILAHsGPSVDLAIFSLHLAGISSILGAINFITTIFNMRaPGMTLEKMPLFVWSVLITAFLLLLSLPVLAGAITMLLT 202

                          90       100
                  ....*....|....*....|....
gi 2205982155  79 DRHFNTSFFHPGGGGDPVLFQHLF 102
Cdd:cd01663   203 DRNFNTSFFDPAGGGDPILYQHLF 226

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2205982155   1 LSVYTFH-GKSVDLSILALHLAGVGSLTGAINTVCSSTRLR-RDYRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLT 78
Cdd:MTH00153  130 LSSNIAHsGASVDLAIFSLHLAGISSILGAINFITTIINMRsKGMTLDRMPLFVWSVLITAILLLLSLPVLAGAITMLLT 209

                          90       100
                  ....*....|....*....|....
gi 2205982155  79 DRHFNTSFFHPGGGGDPVLFQHLF 102
Cdd:MTH00153  210 DRNLNTSFFDPAGGGDPILYQHLF 233

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2205982155   8 GKSVDLSILALHLAGVGSLTGAINTVCSSTRLR-RDYRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLTDRHFNTSF 86
Cdd:MTH00167  140 GASVDLAIFSLHLAGVSSILGSINFITTIINMKpPGITQYQTPLFVWSILVTTILLLLSLPVLAAAITMLLTDRNLNTTF 219

                          90
                  ....*....|....*.
gi 2205982155  87 FHPGGGGDPVLFQHLF 102
Cdd:MTH00167  220 FDPAGGGDPILYQHLF 235

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 2205982155   1 LSVYTFH-GKSVDLSILALHLAGVGSLTGAINTVCSSTRLRRD-YRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLT 78
Cdd:cd00919   120 LSTLSYSsGVGVDLAILGLHLAGVSSILGAINFITTILNMRAPgMTLDKMPLFVWSVLVTAILLLLALPVLAAALVMLLL 199

                          90       100
                  ....*....|....*....|....
gi 2205982155  79 DRHFNTSFFHPGGGGDPVLFQHLF 102
Cdd:cd00919   200 DRNFGTSFFDPAGGGDPVLYQHLF 223

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2205982155   8 GKSVDLSILALHLAGVGSLTGAINTVCSSTRLR-RDYRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLTDRHFNTSF 86
Cdd:MTH00077  140 GASVDLTIFSLHLAGVSSILGAINFITTSINMKpPSMSQYQTPLFVWSVLITAVLLLLSLPVLAAGITMLLTDRNLNTTF 219

                          90
                  ....*....|....*.
gi 2205982155  87 FHPGGGGDPVLFQHLF 102
Cdd:MTH00077  220 FDPAGGGDPVLYQHLF 235

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2205982155   2 SVYTFHGKSVDLSILALHLAGVGSLTGAINTVCSSTRLRR-DYRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLTDR 80
Cdd:MTH00182  136 SIQAHSGGAVDMAIFSLHLAGVSSILGAINFITTIFNMRApGVTFNRLPLFVWSILITAFLLLLSLPVLAGAITMLLTDR 215

                          90       100
                  ....*....|....*....|..
gi 2205982155  81 HFNTSFFHPGGGGDPVLFQHLF 102
Cdd:MTH00182  216 NFNTTFFDPAGGGDPILFQHLF 237

cytochrome c oxidase subunit I; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2205982155   8 GKSVDLSILALHLAGVGSLTGAINTVCSSTRLRRD-YRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLTDRHFNTSF 86
Cdd:MTH00103  140 GASVDLTIFSLHLAGVSSILGAINFITTIINMKPPaMSQYQTPLFVWSVLITAVLLLLSLPVLAAGITMLLTDRNLNTTF 219

                          90
                  ....*....|....*.
gi 2205982155  87 FHPGGGGDPVLFQHLF 102
Cdd:MTH00103  220 FDPAGGGDPILYQHLF 235

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2205982155   2 SVYTFHGKSVDLSILALHLAGVGSLTGAINTVCSSTRLRR-DYRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLTDR 80
Cdd:MTH00026  135 SIQAHSGGSVDMAIFSLHLAGLSSILGAMNFITTVMNMRTpGMTMSRIPLFVWSVFITAILLLLSLPVLAGAITMLLTDR 214

                          90       100
                  ....*....|....*....|..
gi 2205982155  81 HFNTSFFHPGGGGDPVLFQHLF 102
Cdd:MTH00026  215 NFNTTFFDPAGGGDPILYQHLF 236

cytochrome c oxidase subunit I; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2205982155   2 SVYTFHGKSVDLSILALHLAGVGSLTGAINTVCSSTRLRRDYRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLTDRH 81
Cdd:MTH00048  133 SSLFSSSWGVDFLMFSLHLAGVSSLFGSINFICTIYSAFMTNVFSRTSIILWSYLFTSILLLLSLPVLAAAITMLLFDRN 212

                          90       100
                  ....*....|....*....|.
gi 2205982155  82 FNTSFFHPGGGGDPVLFQHLF 102
Cdd:MTH00048  213 FGSAFFDPLGGGDPVLFQHMF 233

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 2205982155  11 VDLSILALHLAGVGSLTGAINTVCSSTRLRRDYRMVKMPVFTVSVTVTGHMLILALPVLGAGLTMLLTDRHFNTsffhpg 90
Cdd:pfam00115 118 VDLWYIGLLLAGVSSLLGAINFIVTILKRRAPGMTLRMPLFVWAILATAILILLAFPVLAAALLLLLLDRSLGA------ 191

                          90
                  ....*....|..
gi 2205982155  91 GGGDPVLFQHLF 102
Cdd:pfam00115 192 GGGDPLLDQHLF 203