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 195996401   5 VGDKIPS--YRLQQGSPGNNVDIAELVANKKAIIFGVPGAFTPGCHRSHLPGYVADYDKIVAKGVDIIICVSVNDAFVVD 82
Cdd:cd03013    1 VGDKLPNvtLFEYVPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 195996401  83 AWGKSVGAENKVVMLADPVAAFTKAIGMDLDATPILGNIRSKRYSMILSDGVLTNLNVEPDGTGLTCSLSNSILS 157
Cdd:cd03013   81 AWGKALGAKDKIRFLADGNGEFTKALGLTLDLSAAGGGIRSKRYALIVDDGKVKYLFVEEDPGDVEVSSAENVLK 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 195996401   5 VGDKIPS--YRLQQGSPGNNVDIAELVANKKAIIFGVPGAFTPGCHRSHLPGYVADYDKIVAKGVDIIICVSVNDAFVVD 82
Cdd:cd03013    1 VGDKLPNvtLFEYVPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 195996401  83 AWGKSVGAENKVVMLADPVAAFTKAIGMDLDATPILGNIRSKRYSMILSDGVLTNLNVEPDGTGLTCSLSNSILS 157
Cdd:cd03013   81 AWGKALGAKDKIRFLADGNGEFTKALGLTLDLSAAGGGIRSKRYALIVDDGKVKYLFVEEDPGDVEVSSAENVLK 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 195996401   8 KIPSYRLQqGSPGNNVDIAELvANKKAIIFGVPGAFTPGCHRShLPGYVADYDKIvAKGVDIIICVSVNDAFVVDAWGKS 87
Cdd:cd02971    1 KAPDFTLP-ATDGGEVSLSDF-KGKWVVLFFYPKDFTPVCTTE-LCAFRDLAEEF-AKGGAEVLGVSVDSPFSHKAWAEK 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 195996401  88 VGAENkVVMLADPVAAFTKAIGMDLDATPilGNIRSKRYSMILS-DGVLTNLNVEPDGTG 146
Cdd:cd02971   77 EGGLN-FPLLSDPDGEFAKAYGVLIEKSA--GGGLAARATFIIDpDGKIRYVEVEPLPTG 133

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 195996401   3 IAVGDKIPSYRL--QQGSPgnnVDIAELVANKKAIIFGVPGAFTPGChRSHLPGYVADYDKIVAKGVdIIICVSVNDAFV 80
Cdd:cd03018    1 LEVGDKAPDFELpdQNGQE---VRLSEFRGRKPVVLVFFPLAFTPVC-TKELCALRDSLELFEAAGA-EVLGISVDSPFS 75

                 ....*....
gi 195996401  81 VDAWGKSVG 89
Cdd:cd03018   76 LRAWAEENG 84