Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold; The thioredoxin (TRX)-like superfamily is a large, diverse group of proteins containing a TRX fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include the families of TRX, protein disulfide isomerase (PDI), tlpA, glutaredoxin, NrdH redoxin, and bacterial Dsb proteins (DsbA, DsbC, DsbG, DsbE, DsbDgamma). Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins, glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 497534700  164 APEHKEQESITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVSLRAISGRTTVPQVFIGGKHIGGSEELEAFLG 242
Cdd:TIGR02190   1 APQARKPESVVVFTKPGCPFCAKAKATLKEKGYDFEEIPLGNDARGRSLRAVTGATTVPQVFIGGKLIGGSDELEAYLA 79

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 497534700   6 EGQSIPQVTFPTRQGDAWVNVTTEELFKDKTVIVFSLPGAFTPTCSSSHLPRYNELHSVFKDNGVDDILCVSVNDTFVMN 85
Cdd:cd03013    1 VGDKLPNVTLFEYVPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 497534700  86 AWKADQEA-EKITFIPDGNGDFTDGMGMLVEKNDIGFGKRSWRYSMLVKNGVVEKMFIEEDvpGDPFKVSDADTML 160
Cdd:cd03013   81 AWGKALGAkDKIRFLADGNGEFTKALGLTLDLSAAGGGIRSKRYALIVDDGKVKYLFVEED--PGDVEVSSAENVL 154

Glutaredoxin (GRX) family, PRX5 hybrid subfamily; composed of hybrid proteins containing peroxiredoxin (PRX) and GRX domains, which is found in some pathogenic bacteria and cyanobacteria. PRXs are thiol-specific antioxidant (TSA) proteins that 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. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins. PRX-GRX hybrid proteins from Haemophilus influenza and Neisseria meningitis exhibit GSH-dependent peroxidase activity. The flow of reducing equivalents in the catalytic cycle of the hybrid protein goes from NADPH -> GSH reductase -> GSH -> GRX domain of hybrid -> PRX domain of hybrid -> peroxide substrate.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 497534700 171 ESITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVSLRAISGRTTVPQVFIGGKHIGGSEELEAFL 241
Cdd:cd03029    1 ESVSLFTKPGCPFCARAKAALQENGISYEEIPLGKDITGRSLRAVTGAMTVPQVFIDGELIGGSDDLEKYF 71

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 497534700 173 ITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVS-LRAISGRTTVPQVFIGGKHIGG--SEELEAFLG 242
Cdd:COG0695    2 VTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREeLRERSGRRTVPVIFIGGEHLGGfdEGELDALLA 74

glutaredoxin 3; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 497534700 172 SITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVS-LRAISGRTTVPQVFIGGKHIGGSEELEA 239
Cdd:PRK10638   3 NVEIYTKATCPFCHRAKALLNSKGVSFQEIPIDGDAAKREeMIKRSGRTTVPQIFIDAQHIGGCDDLYA 71

putative peroxiredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497534700   5 KEGQSIPQVTFPTRQGdawvnVTTEELFKDKTVIVFSLPGAFTPTCSSSHLP---RYNElhsvFKDNGVdDILCVSVNDT 81
Cdd:PRK13190   3 KLGQKAPDFTVNTTKG-----PIDLSKYKGKWVLLFSHPADFTPVCTTEFIAfsrRYED----FKKLGV-ELVGLSVDSI 72

                         90
                 ....*....|.
gi 497534700  82 FVMNAWKADQE 92
Cdd:PRK13190  73 YSHIAWLRDIE 83

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 497534700   6 EGQSIPQVTFPTRQGDAWVNVTTEELFKDKTVIVFSLPGAFTPTCSSSHLPRYNELHSVFKDNGVDDILCVSVNDTFVMN 85
Cdd:cd03013    1 VGDKLPNVTLFEYVPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 497534700  86 AWKADQEA-EKITFIPDGNGDFTDGMGMLVEKNDIGFGKRSWRYSMLVKNGVVEKMFIEEDvpGDPFKVSDADTML 160
Cdd:cd03013   81 AWGKALGAkDKIRFLADGNGEFTKALGLTLDLSAAGGGIRSKRYALIVDDGKVKYLFVEED--PGDVEVSSAENVL 154

Glutaredoxin (GRX) family, PRX5 hybrid subfamily; composed of hybrid proteins containing peroxiredoxin (PRX) and GRX domains, which is found in some pathogenic bacteria and cyanobacteria. PRXs are thiol-specific antioxidant (TSA) proteins that 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. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins. PRX-GRX hybrid proteins from Haemophilus influenza and Neisseria meningitis exhibit GSH-dependent peroxidase activity. The flow of reducing equivalents in the catalytic cycle of the hybrid protein goes from NADPH -> GSH reductase -> GSH -> GRX domain of hybrid -> PRX domain of hybrid -> peroxide substrate.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 497534700 171 ESITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVSLRAISGRTTVPQVFIGGKHIGGSEELEAFL 241
Cdd:cd03029    1 ESVSLFTKPGCPFCARAKAALQENGISYEEIPLGKDITGRSLRAVTGAMTVPQVFIDGELIGGSDDLEKYF 71

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 497534700  10 IPQVTFPTRQGDawvNVTTEElFKDKTVIVFSLPGAFTPTCSSShLPRYNELHSVFKDNGVDdILCVSVNDTFVMNAWKA 89
Cdd:cd02971    2 APDFTLPATDGG---EVSLSD-FKGKWVVLFFYPKDFTPVCTTE-LCAFRDLAEEFAKGGAE-VLGVSVDSPFSHKAWAE 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 497534700  90 DQEAEKITFIPDGNGDFTDGMGMLVEKNDigFGKRSWRYSMLV-KNGVVEKMFIEEDVpgdpfKVSDADTML 160
Cdd:cd02971   76 KEGGLNFPLLSDPDGEFAKAYGVLIEKSA--GGGLAARATFIIdPDGKIRYVEVEPLP-----TGRNAEELL 140

Glutaredoxin (GRX) family; composed of GRX, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, as well as E. coli GRX1 and GRX3, which are members of this family. E. coli GRX2, however, is a 24-kDa protein that belongs to the GSH S-transferase (GST) family.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 497534700 173 ITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVS-LRAISGRTTVPQVFIGGKHIGGSEELEA 239
Cdd:cd02066    2 VVVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDGELREeLKELSGWPTVPQIFINGEFIGGYDDLKA 69

Glutaredoxin, GrxC family; Glutaredoxins are thioltransferases (disulfide reductases) which utilize glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system. Glutaredoxins utilize the CXXC motif common to thioredoxins and are involved in multiple cellular processes including protection from redox stress, reduction of critical enzymes such as ribonucleotide reductase and the generation of reduced sulfur for iron sulfur cluster formation. Glutaredoxins are capable of reduction of mixed disulfides of glutathione as well as the formation of glutathione mixed disulfides. This family of glutaredoxins includes the E. coli protein GrxC (Grx3) which appears to have a secondary role in reducing ribonucleotide reductase (in the absence of GrxA) possibly indicating a role in the reduction of other protein disulfides. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 497534700  173 ITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDAttvSLRAI----SGRTTVPQVFIGGKHIGGSEELEA 239
Cdd:TIGR02181   1 VTIYTKPYCPYCTRAKALLSSKGVTFTEIRVDGDP---ALRDEmmqrSGRRTVPQIFIGDVHVGGCDDLYA 68

Glutaredoxin (GRX) family, GRX human class 1 and 2 (h_1_2)-like subfamily; composed of proteins similar to human GRXs, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, which are members of this subfamily. Also included in this subfamily are the N-terminal GRX domains of proteins similar to human thioredoxin reductase 1 and 3.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 497534700 173 ITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVS----LRAISGRTTVPQVFIGGKHIGGSEELEA 239
Cdd:cd03419    2 VVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEiqdyLQELTGQRTVPNVFIGGKFIGGCDDLMA 72

Glutaredoxin; Glutaredoxins are thioltransferases (disulfide reductases) which utilize glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system. Glutaredoxins utilize the CXXC motif common to thioredoxins and are involved in multiple cellular processes including protection from redox stress, reduction of critical enzymes such as ribonucleotide reductase and the generation of reduced sulfur for iron sulfur cluster formation. Glutaredoxins are capable of reduction of mixed disulfides of glutathione as well as the formation of glutathione mixed disulfides. This model represents eukaryotic glutaredoxins and includes sequences from fungi, plants and metazoans as well as viruses.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 497534700  173 ITVFTKPGCPFCMKAKQNLIDKGLNYEEVV-LGKDATTVSLRA----ISGRTTVPQVFIGGKHIGGSEELEA 239
Cdd:TIGR02180   1 VVVFSKSYCPYCKKAKEILAKLNVKPYEVVeLDQLSNGSEIQDyleeITGQRTVPNIFINGKFIGGCSDLLA 72

Glutaredoxin (GRX) family, Dishevelled, Egl-10, and Pleckstrin (DEP) subfamily; composed of uncharacterized proteins containing a GRX domain and additional domains DEP and DUF547, both of which have unknown functions. GRX is a glutathione (GSH) dependent reductase containing a redox active CXXC motif in a TRX fold. It has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. By altering the redox state of target proteins, GRX is involved in many cellular functions.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 497534700 173 ITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDAT-TVSLRAISGRTTVPQVFIGGKHIGGSEELE 238
Cdd:cd03027    3 VTIYSRLGCEDCTAVRLFLREKGLPYVEINIDIFPErKAELEERTGSSVVPQIFFNEKLVGGLTDLK 69

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497534700   7 GQSIPQVTFPTRQGDAWVNVTTEElFKDKTVIVFSLPGAFTPTCSSshlprynELHSV------FKDNGVdDILCVSVND 80
Cdd:COG0450    6 GDKAPDFTAEATHGGEFKKISLSD-YKGKWVVLFFHPADFTFVCPT-------ELGAFakryeeFKKLGV-EVIGLSVDS 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 497534700  81 TFVMNAWKAD----QEAEKITF--IPDGNGDFTDGMGMLVEKN 117
Cdd:COG0450   77 VFSHKAWHETikekGGIVKIKFpiIADPTGKIARAYGMLHPED 119

Uxx-star family glutaredoxin-like (seleno)protein; A number of proteins with glutaredoxin-like folds, a length of about 75 amino acids, and a CxxC, C/UxxT, or CxxS motif near the N-terminus end with a UXX-COOH motif. That final motif typically is missed during coding region feature prediction by genome annotation pipelines. This HMM covers proteins from several distinctive families with this feature. The seed alignment illustrates the final selenocysteine or aligned Cys or Ser residues, but the HMM also hits proteins that lack an equivalent motif at the C-terminus. This C-terminal selenocysteine-containing motif has not yet been described in the literature.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 497534700 173 ITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVS--LRAISGRTTVPQVFIGGK 229
Cdd:NF041212   1 VVIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEemLRLTGGERIVPVIVEGGE 59

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 497534700   5 KEGQSIPQVTFPTRQGDAwvnVTTEELFKDKTVIVFSLPGAFTPTCsSSHLPRYNELHSVFKDNGVdDILCVSVNDTFVM 84
Cdd:cd03018    2 EVGDKAPDFELPDQNGQE---VRLSEFRGRKPVVLVFFPLAFTPVC-TKELCALRDSLELFEAAGA-EVLGISVDSPFSL 76

                         90
                 ....*....|....
gi 497534700  85 NAWKadqEAEKITF 98
Cdd:cd03018   77 RAWA---EENGLTF 87

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 497534700  176 FTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVSLRAISGRTTVPQVFIGGKHIGGSEEL 237
Cdd:pfam13417   2 YGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPLGKVPVLEDDGGILCESLAI 63

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 497534700  28 TEELFKDKTVIVFSLPGAFTPTCsSSHLPRYNELHSVFKDNGVdDILCVSVNDTFVMNAWKADQEAE------KITFIPD 101
Cdd:cd03015   23 SLSDYKGKWVVLFFYPLDFTFVC-PTEIIAFSDRYEEFKKLNA-EVLGVSTDSHFSHLAWRNTPRKEgglgkiNFPLLAD 100

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 497534700 102 GNGDFTDGMGMLVEKNDIgfgkrSWRYSMLV-KNGVV 137
Cdd:cd03015  101 PKKKISRDYGVLDEEEGV-----ALRGTFIIdPEGII 132

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 497534700   7 GQSIPQVTFPTRQGdawvNVTTEELFKDKTVIVFSLPGAFTPTCsSSHLPRYNELHSVFKDNGVdDILCVSVNDTFVMNA 86
Cdd:cd03016    2 GDTAPNFEADTTHG----PIKFHDYLGDSWGILFSHPADFTPVC-TTELGAFAKLAPEFKKRNV-KLIGLSVDSVESHIK 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 497534700  87 WKADQEA---EKITF--IPDGNGDFTDGMGMLVEKNDIGFGKRS 125
Cdd:cd03016   76 WIEDIEEytgVEIPFpiIADPDREVAKLLGMIDPDAGSTLTVRA 119

bifunctional gluaredoxin/ribonucleoside-diphosphate reductase subunit beta; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 497534700 173 ITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVSLRAISGRT---------TVPQVFIGGKHIGGSEELEAFLG 242
Cdd:PRK12759   4 VRIYTKTNCPFCDLAKSWFGANDIPFTQISLDDDVKRAEFYAEVNKNillveehirTVPQIFVGDVHIGGYDNLMARAG 82

Arsenate Reductase (ArsC) family, Spx subfamily; Spx is a unique RNA polymerase (RNAP)-binding protein present in bacilli and some mollicutes. It inhibits transcription by binding to the C-terminal domain of the alpha subunit of RNAP, disrupting complex formation between RNAP and certain transcriptional activator proteins like ResD and ComA. In response to oxidative stress, Spx can also activate transcription, making it a general regulator that exerts both positive and negative control over transcription initiation. Spx has been shown to exert redox-sensitive transcriptional control over genes like trxA (TRX) and trxB (TRX reductase), genes that function in thiol homeostasis. This redox-sensitive activity is dependent on the presence of a CXXC motif, present in some members of the Spx subfamily, that acts as a thiol/disulfide switch. Spx has also been shown to repress genes in a sulfate-dependent manner independent of the presence of the CXXC motif.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 497534700 173 ITVFTKPGCPFCMKAKQNLIDKGLNYEEVVLGKDATTVS 211
Cdd:cd03032    2 IKLYTSPSCSSCRKAKQWLEEHQIPFEERNLFKQPLTKE 40

putative peroxiredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497534700   5 KEGQSIPQVTFPTRQGdawvnVTTEELFKDKTVIVFSLPGAFTPTCSSSHLP---RYNElhsvFKDNGVdDILCVSVNDT 81
Cdd:PRK13190   3 KLGQKAPDFTVNTTKG-----PIDLSKYKGKWVLLFSHPADFTPVCTTEFIAfsrRYED----FKKLGV-ELVGLSVDSI 72

                         90
                 ....*....|.
gi 497534700  82 FVMNAWKADQE 92
Cdd:PRK13190  73 YSHIAWLRDIE 83

DsbA family, DsbC and DsbG subfamily; V-shaped homodimeric proteins containing a redox active CXXC motif imbedded in a TRX fold. They function as protein disulfide isomerases and chaperones in the bacterial periplasm to correct non-native disulfide bonds formed by DsbA and prevent aggregation of incorrectly folded proteins. DsbC and DsbG are kept in their reduced state by the cytoplasmic membrane protein DsbD, which utilizes the TRX/TRX reductase system in the cytosol as a source of reducing equivalents. DsbG differ from DsbC in that it has a more limited substrate specificity, and it may preferentially act later in the folding process to catalyze disulfide rearrangements in folded or partially folded proteins. Also included in the alignment is the predicted protein TrbB, whose gene was sequenced from the enterohemorrhagic E. coli type IV pilus gene cluster, which is required for efficient plasmid transfer.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 497534700 149 DPFKVSDADTMLNYIAPEHKEQesITVFTKPGCPFCMKAKQNLIDKGLNYE 199
Cdd:cd03020   59 IDLSALPLDDAIVYGKGNGKRV--VYVFTDPDCPYCRKLEKELKPNADGVT 107