Peroxiredoxin (PRX) family, PRX5-like subfamily; members are similar to the human protein, PRX5, a homodimeric TRX peroxidase, widely expressed in tissues and found cellularly in mitochondria, peroxisomes and the cytosol. The cellular location of PRX5 suggests that it may have an important antioxidant role in organelles that are major sources of reactive oxygen species (ROS), as well as a role in the control of signal transduction. PRX5 has been shown to reduce hydrogen peroxide, alkyl hydroperoxides and peroxynitrite. As with all other PRXs, the N-terminal peroxidatic cysteine of PRX5 is oxidized into a sulfenic acid intermediate upon reaction with peroxides. Human PRX5 is able to resolve this intermediate by forming an intramolecular disulfide bond with its C-terminal cysteine (the resolving cysteine), which can then be reduced by TRX, just like an atypical 2-cys PRX. This resolving cysteine, however, is not conserved in other members of the subfamily. In such cases, it is assumed that the oxidized cysteine is directly resolved by an external small-molecule or protein reductant, typical of a 1-cys PRX. In the case of the H. influenza PRX5 hybrid, the resolving glutaredoxin domain is on the same protein chain as PRX. PRX5 homodimers show an A-type interface, similar to atypical 2-cys PRXs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355    6 VGDAIPAVEVFE--GEPGNKVNLAELFKGKKGVLFGVPGAFTPGCSKTHLPGFVEQAEALKAKGVQVVACLSVNDAFVTG 83
Cdd:cd03013   1 VGDKLPNVTLFEyvPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6746355   84 EWGRAHKAEGKVRLLADPTGAFGKETDLLLDDSLvsIFGNRRLKRFSMVVQDGIVKALNVEPDGTGLTCSLAPNIIS 160
Cdd:cd03013  81 AWGKALGAKDKIRFLADGNGEFTKALGLTLDLSA--AGGGIRSKRYALIVDDGKVKYLFVEEDPGDVEVSSAENVLK 155

Peroxiredoxin (PRX) family, PRX5-like subfamily; members are similar to the human protein, PRX5, a homodimeric TRX peroxidase, widely expressed in tissues and found cellularly in mitochondria, peroxisomes and the cytosol. The cellular location of PRX5 suggests that it may have an important antioxidant role in organelles that are major sources of reactive oxygen species (ROS), as well as a role in the control of signal transduction. PRX5 has been shown to reduce hydrogen peroxide, alkyl hydroperoxides and peroxynitrite. As with all other PRXs, the N-terminal peroxidatic cysteine of PRX5 is oxidized into a sulfenic acid intermediate upon reaction with peroxides. Human PRX5 is able to resolve this intermediate by forming an intramolecular disulfide bond with its C-terminal cysteine (the resolving cysteine), which can then be reduced by TRX, just like an atypical 2-cys PRX. This resolving cysteine, however, is not conserved in other members of the subfamily. In such cases, it is assumed that the oxidized cysteine is directly resolved by an external small-molecule or protein reductant, typical of a 1-cys PRX. In the case of the H. influenza PRX5 hybrid, the resolving glutaredoxin domain is on the same protein chain as PRX. PRX5 homodimers show an A-type interface, similar to atypical 2-cys PRXs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355    6 VGDAIPAVEVFE--GEPGNKVNLAELFKGKKGVLFGVPGAFTPGCSKTHLPGFVEQAEALKAKGVQVVACLSVNDAFVTG 83
Cdd:cd03013   1 VGDKLPNVTLFEyvPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6746355   84 EWGRAHKAEGKVRLLADPTGAFGKETDLLLDDSLvsIFGNRRLKRFSMVVQDGIVKALNVEPDGTGLTCSLAPNIIS 160
Cdd:cd03013  81 AWGKALGAKDKIRFLADGNGEFTKALGLTLDLSA--AGGGIRSKRYALIVDDGKVKYLFVEEDPGDVEVSSAENVLK 155

Redoxin; This family of redoxins includes peroxiredoxin, thioredoxin and glutaredoxin proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355      5 KVGDAIPAVEVFE-GEPGNKVNLAElFKGKKGVLFGVPGAFTPGCSKTHlPGFVEQAEALKAKGVQVVACLSVNDAF-VT 82
Cdd:pfam08534   1 KAGDKAPDFTLPDaATDGNTVSLSD-FKGKKVVLNFWPGAFCPTCSAEH-PYLEKLNELYKEKGVDVVAVNSDNDAFfVK 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6746355     83 GEWGRAHkaeGKVRLLADPTGAFGKETDLLLDDSLVSifgNRRLKRFSMVVQDGIVKALNVEPDGT 148
Cdd:pfam08534  79 RFWGKEG---LPFPFLSDGNAAFTKALGLPIEEDASA---GLRSPRYAVIDEDGKVVYLFVGPEPG 138

Peroxiredoxin (PRX) family, PRX5-like subfamily; members are similar to the human protein, PRX5, a homodimeric TRX peroxidase, widely expressed in tissues and found cellularly in mitochondria, peroxisomes and the cytosol. The cellular location of PRX5 suggests that it may have an important antioxidant role in organelles that are major sources of reactive oxygen species (ROS), as well as a role in the control of signal transduction. PRX5 has been shown to reduce hydrogen peroxide, alkyl hydroperoxides and peroxynitrite. As with all other PRXs, the N-terminal peroxidatic cysteine of PRX5 is oxidized into a sulfenic acid intermediate upon reaction with peroxides. Human PRX5 is able to resolve this intermediate by forming an intramolecular disulfide bond with its C-terminal cysteine (the resolving cysteine), which can then be reduced by TRX, just like an atypical 2-cys PRX. This resolving cysteine, however, is not conserved in other members of the subfamily. In such cases, it is assumed that the oxidized cysteine is directly resolved by an external small-molecule or protein reductant, typical of a 1-cys PRX. In the case of the H. influenza PRX5 hybrid, the resolving glutaredoxin domain is on the same protein chain as PRX. PRX5 homodimers show an A-type interface, similar to atypical 2-cys PRXs.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355    6 VGDAIPAVEVFE--GEPGNKVNLAELFKGKKGVLFGVPGAFTPGCSKTHLPGFVEQAEALKAKGVQVVACLSVNDAFVTG 83
Cdd:cd03013   1 VGDKLPNVTLFEyvPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6746355   84 EWGRAHKAEGKVRLLADPTGAFGKETDLLLDDSLvsIFGNRRLKRFSMVVQDGIVKALNVEPDGTGLTCSLAPNIIS 160
Cdd:cd03013  81 AWGKALGAKDKIRFLADGNGEFTKALGLTLDLSA--AGGGIRSKRYALIVDDGKVKYLFVEEDPGDVEVSSAENVLK 155

Peroxiredoxin (PRX) family; composed of the different classes of PRXs including many proteins originally known as bacterioferritin comigratory proteins (BCP), based on their electrophoretic mobility before their function was identified. PRXs are thiol-specific antioxidant (TSA) proteins also known as TRX peroxidases and alkyl hydroperoxide reductase C22 (AhpC) proteins. They confer a protective antioxidant role in cells through their peroxidase activity in which hydrogen peroxide, peroxynitrate, and organic hydroperoxides are reduced and detoxified using reducing equivalents derived from either TRX, glutathione, trypanothione and AhpF. They are distinct from other peroxidases in that they have no cofactors such as metals or prosthetic groups. The first step of catalysis, common to all PRXs, is the nucleophilic attack by the catalytic cysteine (also known as the peroxidatic cysteine) on the peroxide leading to cleavage of the oxygen-oxygen bond and the formation of a cysteine sulfenic acid intermediate. The second step of the reaction, the resolution of the intermediate, distinguishes the different types of PRXs. The presence or absence of a second cysteine (the resolving cysteine) classifies PRXs as either belonging to the 2-cys or 1-cys type. The resolving cysteine of 2-cys PRXs is either on the same chain (atypical) or on the second chain (typical) of a functional homodimer. Structural and motif analysis of this growing family supports the need for a new classification system. The peroxidase activity of PRXs is regulated in vivo by irreversible cysteine over-oxidation into a sulfinic acid, phosphorylation and limited proteolysis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355   10 IPAVEVFeGEPGNKVNLAElFKGKKGVLFGVPGAFTPGCSkTHLPGFVEQAEALKAKGVQVVaCLSVNDAFVTGEWGRAH 89
Cdd:cd02971   2 APDFTLP-ATDGGEVSLSD-FKGKWVVLFFYPKDFTPVCT-TELCAFRDLAEEFAKGGAEVL-GVSVDSPFSHKAWAEKE 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6746355   90 KaEGKVRLLADPTGAFGKETDLLLDDSlvsiFGNRRLKRFSMVV-QDGIVKALNVEPDGTG 149
Cdd:cd02971  78 G-GLNFPLLSDPDGEFAKAYGVLIEKS----AGGGLAARATFIIdPDGKIRYVEVEPLPTG 133

AhpC/TSA family; This family contains proteins related to alkyl hydroperoxide reductase (AhpC) and thiol specific antioxidant (TSA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355      6 VGDAIPAVEVFEGEpGNKVNLAElFKGKKGVLFGVPGAFTPGCsKTHLPGFVEQAEALKAKGVQVVAcLSVNDAFVTGEW 85
Cdd:pfam00578   1 VGDKAPDFELPDGD-GGTVSLSD-YRGKWVVLFFYPADWTPVC-TTELPALADLYEEFKKLGVEVLG-VSVDSPESHKAF 76

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 6746355     86 GRAHKAegKVRLLADPTGAFGKETDLLLDDSLVSI 120
Cdd:pfam00578  77 AEKYGL--PFPLLSDPDGEVARAYGVLNEEEGGAL 109

Peroxiredoxin (PRX) family, AhpE-like subfamily; composed of proteins similar to Mycobacterium tuberculosis AhpE. AhpE is described as a 1-cys PRX because of the absence of a resolving cysteine. The structure and sequence of AhpE, however, show greater similarity to 2-cys PRXs than 1-cys PRXs. PRXs are thiol-specific antioxidant (TSA) proteins that confer a protective role in cells through their peroxidase activity in which hydrogen peroxide, peroxynitrate, and organic hydroperoxides are reduced and detoxified using reducing equivalents derived from either thioredoxin, glutathione, trypanothione and AhpF. The first step of catalysis is the nucleophilic attack by the peroxidatic cysteine on the peroxide leading to the formation of a cysteine sulfenic acid intermediate. The absence of a resolving cysteine suggests that functional AhpE is regenerated by an external reductant. The solution behavior and crystal structure of AhpE show that it forms dimers and octamers.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355    4 IKVGDAIPAVEVfEGEPGNKVNLAELFKGKKGVLFGVPGAFTPGCSKtHLPGFVEQAEALKAKGVQVVAcLSVNDAFVTG 83
Cdd:cd03018   1 LEVGDKAPDFEL-PDQNGQEVRLSEFRGRKPVVLVFFPLAFTPVCTK-ELCALRDSLELFEAAGAEVLG-ISVDSPFSLR 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6746355   84 EWGRAHKAEgkVRLLAD--PTGAFGKETDLLLDDSLVSifgnrrlKRFSMVV-QDGIVKALNVEPDG 147
Cdd:cd03018  78 AWAEENGLT--FPLLSDfwPHGEVAKAYGVFDEDLGVA-------ERAVFVIdRDGIIRYAWVSDDG 135

Peroxiredoxin (PRX) family, Typical 2-Cys PRX subfamily; PRXs are thiol-specific antioxidant (TSA) proteins, which confer a protective role in cells through its peroxidase activity by reducing hydrogen peroxide, peroxynitrite, and organic hydroperoxides. The functional unit of typical 2-cys PRX is a homodimer. A unique intermolecular redox-active disulfide center is utilized for its activity. Upon reaction with peroxides, its peroxidatic cysteine is oxidized into a sulfenic acid intermediate which is resolved by bonding with the resolving cysteine from the other subunit of the homodimer. This intermolecular disulfide bond is then reduced by thioredoxin, tryparedoxin or AhpF. Typical 2-cys PRXs, like 1-cys PRXs, form decamers which are stabilized by reduction of the active site cysteine. Typical 2-cys PRX interacts through beta strands at one edge of the monomer (B-type interface) to form the functional homodimer, and uses an A-type interface (similar to the dimeric interface in atypical 2-cys PRX and PRX5) at the opposite end of the monomer to form the stable decameric (pentamer of dimers) structure.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355    6 VGDAIPAVE---VFEGEPGNKVNLAElFKGKKGVLFGVPGAFTPGCSkTHLPGFVEQAEALKAKGVQVVAClSVNDAFVT 82
Cdd:cd03015   1 VGKKAPDFKataVVPNGEFKEISLSD-YKGKWVVLFFYPLDFTFVCP-TEIIAFSDRYEEFKKLNAEVLGV-STDSHFSH 77

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 6746355   83 GEWGRAHKAEGKVR-----LLADPTGAFGKETDLLLDD 115
Cdd:cd03015  78 LAWRNTPRKEGGLGkinfpLLADPKKKISRDYGVLDEE 115

Peroxiredoxin (PRX) family, 1-cys PRX subfamily; composed of PRXs containing only one conserved cysteine, which serves as the peroxidatic cysteine. They are homodimeric thiol-specific antioxidant (TSA) proteins that confer a protective role in cells by reducing and detoxifying hydrogen peroxide, peroxynitrite, and organic hydroperoxides. As with all other PRXs, a cysteine sulfenic acid intermediate is formed upon reaction of 1-cys PRX with its substrates. Having no resolving cysteine, the oxidized enzyme is resolved by an external small-molecule or protein reductant such as thioredoxin or glutaredoxin. Similar to typical 2-cys PRX, 1-cys PRX forms a functional dimeric unit with a B-type interface, as well as a decameric structure which is stabilized in the reduced form of the enzyme. Other oligomeric forms, tetramers and hexamers, have also been reported. Mammalian 1-cys PRX is localized cellularly in the cytosol and is expressed at high levels in brain, eye, testes and lung. The seed-specific plant 1-cys PRXs protect tissues from reactive oxygen species during desiccation and are also called rehydrins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355   23 KVNLAELFKGKKGVLFGVPGAFTPGCSkTHLPGFVEQAEALKAKGVQVVAcLSVNDAFVTGEWGRAHKAEGKVRL----L 98
Cdd:cd03016  16 PIKFHDYLGDSWGILFSHPADFTPVCT-TELGAFAKLAPEFKKRNVKLIG-LSVDSVESHIKWIEDIEEYTGVEIpfpiI 93

                        90
                ....*....|....
gi 6746355   99 ADPTGAFGKETDLL 112
Cdd:cd03016  94 ADPDREVAKLLGMI 107

alkyl hydroperoxide reductase subunit C; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355    32 GKKGVLFGVPGAFTPGCSkTHLPGFVEQAEALKAKGVQVVAcLSVNDAFVTGEWGRAHKAEGKVR--LLADPTGAFGKET 109
Cdd:PRK10382  31 GRWSVFFFYPADFTFVCP-TELGDVADHYEELQKLGVDVYS-VSTDTHFTHKAWHSSSETIAKIKyaMIGDPTGALTRNF 108

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 6746355   110 DLLLDDSLVSifgnrrlKRFSMVVQ-DGIVKALNVEPDGTG 149
Cdd:PRK10382 109 DNMREDEGLA-------DRATFVVDpQGIIQAIEVTAEGIG 142

putative peroxiredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355     6 VGDAIPAVEVFEGEpgNKVNLAELFKGKKGVLFGVPGAFTPGCSkTHLPGFVEQAEALKAKGVQVVAcLSVNDAFVTGEW 85
Cdd:PRK13191   9 IGEKFPEMEVITTH--GKIKLPDDYKGRWFVLFSHPGDFTPVCT-TEFYSFAKKYEEFKKLNTELIG-LSVDSNISHIEW 84

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 6746355    86 ----GRAHKAEGKVRLLADPTGAFGKETDLLLDDSLVS 119
Cdd:PRK13191  85 vmwiEKNLKVEVPFPIIADPMGNVAKRLGMIHAESSTA 122

Peroxiredoxin (PRX)-like 1 family; hypothetical proteins that show sequence similarity to PRXs. Members of this group contain a conserved cysteine that aligns to the first cysteine in the CXXC motif of TRX. This does not correspond to the peroxidatic cysteine found in PRXs, which aligns to the second cysteine in the CXXC motif of TRX. In addition, these proteins do not contain the other two conserved residues of the catalytic triad of PRX. PRXs confer a protective antioxidant role in cells through their peroxidase activity in which hydrogen peroxide, peroxynitrate, and organic hydroperoxides are reduced and detoxified using reducing equivalents derived from either thioredoxin, glutathione, trypanothione and AhpF.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6746355   21 GNKVNLAElFKGKKGVLFgvpgAFT-PGC--SKTHLPGFVEQAEALKAKGVQVVAcLSVNDA----FVTGEWGRAHKAEG 93
Cdd:cd02969  14 GKTYSLAD-FADGKALVV----MFIcNHCpyVKAIEDRLNRLAKEYGAKGVAVVA-INSNDIeaypEDSPENMKAKAKEH 87

                        90
                ....*....|....*.
gi 6746355   94 KVR--LLADPTGAFGK 107
Cdd:cd02969  88 GYPfpYLLDETQEVAK 103