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 66773128   5 VGQRLPAVEVQE--EDPGNSLSMAELFSCKRGVLFGVPGAFTPGCSKTHLPGFIQMAGELRAKGVDEVACISVNDVFVMS 82
Cdd:cd03013   1 VGDKLPNVTLFEyvPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 66773128  83 AWGKQNGADGKVRMLADPTGAFTKAVDLVLNnaqLIPVLGNLRSQRYAMLIENGVVTKLSVEPDGTGLTCSLASNFLA 160
Cdd:cd03013  81 AWGKALGAKDKIRFLADGNGEFTKALGLTLD---LSAAGGGIRSKRYALIVDDGKVKYLFVEEDPGDVEVSSAENVLK 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 66773128   5 VGQRLPAVEVQE--EDPGNSLSMAELFSCKRGVLFGVPGAFTPGCSKTHLPGFIQMAGELRAKGVDEVACISVNDVFVMS 82
Cdd:cd03013   1 VGDKLPNVTLFEyvPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 66773128  83 AWGKQNGADGKVRMLADPTGAFTKAVDLVLNnaqLIPVLGNLRSQRYAMLIENGVVTKLSVEPDGTGLTCSLASNFLA 160
Cdd:cd03013  81 AWGKALGAKDKIRFLADGNGEFTKALGLTLD---LSAAGGGIRSKRYALIVDDGKVKYLFVEEDPGDVEVSSAENVLK 155

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66773128     4 KVGQRLPAVEVQEED-PGNSLSMAElFSCKRGVLFGVPGAFTPGCSKTHlPGFIQMAGELRAKGVDEVACISVNDVF-VM 81
Cdd:pfam08534   1 KAGDKAPDFTLPDAAtDGNTVSLSD-FKGKKVVLNFWPGAFCPTCSAEH-PYLEKLNELYKEKGVDVVAVNSDNDAFfVK 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 66773128    82 SAWGKQNgadGKVRMLADPTGAFTKAvdlvLNNAQLIPVLGNLRSQRYAMLIENGVVTKLSVEPDGT 148
Cdd:pfam08534  79 RFWGKEG---LPFPFLSDGNAAFTKA----LGLPIEEDASAGLRSPRYAVIDEDGKVVYLFVGPEPG 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 66773128   5 VGQRLPAVEVQE--EDPGNSLSMAELFSCKRGVLFGVPGAFTPGCSKTHLPGFIQMAGELRAKGVDEVACISVNDVFVMS 82
Cdd:cd03013   1 VGDKLPNVTLFEyvPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 66773128  83 AWGKQNGADGKVRMLADPTGAFTKAVDLVLNnaqLIPVLGNLRSQRYAMLIENGVVTKLSVEPDGTGLTCSLASNFLA 160
Cdd:cd03013  81 AWGKALGAKDKIRFLADGNGEFTKALGLTLD---LSAAGGGIRSKRYALIVDDGKVKYLFVEEDPGDVEVSSAENVLK 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 66773128   8 RLPAVEVQEEDPGN-SLSmaeLFSCKRGVLFGVPGAFTPGCSkTHLPGFIQMAGELrAKGVDEVACISVNDVFVMSAWGK 86
Cdd:cd02971   1 KAPDFTLPATDGGEvSLS---DFKGKWVVLFFYPKDFTPVCT-TELCAFRDLAEEF-AKGGAEVLGVSVDSPFSHKAWAE 75

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 66773128  87 QNGADgKVRMLADPTGAFTKAVDLVLNNAqlipvLGNLRSQRYAMLI-ENGVVTKLSVEPDGTG 149
Cdd:cd02971  76 KEGGL-NFPLLSDPDGEFAKAYGVLIEKS-----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 66773128     5 VGQRLPAVEVQEEDpGNSLSMAElFSCKRGVLFGVPGAFTPGCsKTHLPGFIQMAGELRAKGVdEVACISVNDVFVMSAW 84
Cdd:pfam00578   1 VGDKAPDFELPDGD-GGTVSLSD-YRGKWVVLFFYPADWTPVC-TTELPALADLYEEFKKLGV-EVLGVSVDSPESHKAF 76

                          90       100       110
                  ....*....|....*....|....*....|....
gi 66773128    85 GKQNGAdgKVRMLADPTGAFTKAVDLVLNNAQLI 118
Cdd:pfam00578  77 AEKYGL--PFPLLSDPDGEVARAYGVLNEEEGGA 108

Alkyl hydroperoxide reductase subunit AhpC (peroxiredoxin) [Defense mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66773128   1 MPIKVGQRLPAVEVQ--EEDPGNSLSMAElFSCKRGVLFGVPGAFTPGCSkTHLPGFIQMAGELRAKGVdEVACISVNDV 78
Cdd:COG0450   1 MMPLIGDKAPDFTAEatHGGEFKKISLSD-YKGKWVVLFFHPADFTFVCP-TELGAFAKRYEEFKKLGV-EVIGLSVDSV 77

                        90       100       110
                ....*....|....*....|....*....|....
gi 66773128  79 FVMSAWG---KQNGADGKVR--MLADPTGAFTKA 107
Cdd:COG0450  78 FSHKAWHetiKEKGGIVKIKfpIIADPTGKIARA 111

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 66773128  34 GVLFGVPGAFTPGCSkTHLPGFIQMAGELRAKGVDEVAcISVNDVFVMSAWGK----QNGADGKVRMLADPTGAFTKAVD 109
Cdd:cd03016  28 GILFSHPADFTPVCT-TELGAFAKLAPEFKKRNVKLIG-LSVDSVESHIKWIEdieeYTGVEIPFPIIADPDREVAKLLG 105

                ..
gi 66773128 110 LV 111
Cdd:cd03016 106 MI 107

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 66773128  32 KRGVLFGVPGAFTPGCSkTHLPGFIQMAGELRAKGVdEVACISVNDVFVMSAW---GKQNGADGKVR--MLADPTGAFTK 106
Cdd:cd03015  30 KWVVLFFYPLDFTFVCP-TEIIAFSDRYEEFKKLNA-EVLGVSTDSHFSHLAWrntPRKEGGLGKINfpLLADPKKKISR 107

                ....*..
gi 66773128 107 AVDlVLN 113
Cdd:cd03015 108 DYG-VLD 113