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 521061791  164 APNAKKPLDVTVFTRPGCPFCAKAKGMLKEKGIAFDELVLNKDYRNVTLRAVAGADAVPQVFINGKLIGGSDKLEAWLA 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 521061791   6 EGKPVPNVTFHTRQDNAWVDVSTEQLFKGKTVVVFSLPGAFTPTCSSTHVPRYNQLADALKANGVDDIICMSVNDTFVMN 85
Cdd:cd03013    1 VGDKLPNVTLFEYVPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 521061791  86 EWKAAQEA-DKITFIPDGNGEFTQGMGLLVDKDQLGFGKRSWRYSMLVKDGVVVKMFIEPekDGDPFEVSDADTML 160
Cdd:cd03013   81 AWGKALGAkDKIRFLADGNGEFTKALGLTLDLSAAGGGIRSKRYALIVDDGKVKYLFVEE--DPGDVEVSSAENVL 154

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 521061791    6 EGKPVPNVTFHT-RQDNAWVDVSTeqlFKGKTVVVFSLPGAFTPTCSSTHvPRYNQLADALKANGVDDIICMSVNDTF-V 83
Cdd:pfam08534   2 AGDKAPDFTLPDaATDGNTVSLSD---FKGKKVVLNFWPGAFCPTCSAEH-PYLEKLNELYKEKGVDVVAVNSDNDAFfV 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 521061791   84 MNEWKaaQEADKITFIPDGNGEFTQGMGLLVDKDqLGFGKRSWRYSMLVKDGVVVKMFIEPEKdgdPFEVSDADTML 160
Cdd:pfam08534  78 KRFWG--KEGLPFPFLSDGNAAFTKALGLPIEED-ASAGLRSPRYAVIDEDGKVVYLFVGPEP---GVDVSDAEAVL 148

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 521061791 172 DVTVFTRPGCPFCAKAKGMLKEKGIAFDELVLNKD--YRNVtLRAVAGADAVPQVFINGKLIGG--SDKLEAWLA 242
Cdd:COG0695    1 KVTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDEDpeAREE-LRERSGRRTVPVIFIGGEHLGGfdEGELDALLA 74

glutaredoxin 3; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 521061791 172 DVTVFTRPGCPFCAKAKGMLKEKGIAFDELVLNKDY-RNVTLRAVAGADAVPQVFINGKLIGGSDKLEA 239
Cdd:PRK10638   3 NVEIYTKATCPFCHRAKALLNSKGVSFQEIPIDGDAaKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYA 71

putative peroxiredoxin; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 521061791  32 FKGKTVVVFSLPGAFTPTCSSTHVPRYNQLADALKANgvDDIICMSVNDTFVMNEW 87
Cdd:PRK13191  31 YKGRWFVLFSHPGDFTPVCTTEFYSFAKKYEEFKKLN--TELIGLSVDSNISHIEW 84

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 521061791   6 EGKPVPNVTFHTRQDNAWVDVSTEQLFKGKTVVVFSLPGAFTPTCSSTHVPRYNQLADALKANGVDDIICMSVNDTFVMN 85
Cdd:cd03013    1 VGDKLPNVTLFEYVPGPPNPVNLSELFKGKKVVIFGVPGAFTPTCSAQHLPGYVENADELKAKGVDEVICVSVNDPFVMK 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 521061791  86 EWKAAQEA-DKITFIPDGNGEFTQGMGLLVDKDQLGFGKRSWRYSMLVKDGVVVKMFIEPekDGDPFEVSDADTML 160
Cdd:cd03013   81 AWGKALGAkDKIRFLADGNGEFTKALGLTLDLSAAGGGIRSKRYALIVDDGKVKYLFVEE--DPGDVEVSSAENVL 154

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 521061791    6 EGKPVPNVTFHT-RQDNAWVDVSTeqlFKGKTVVVFSLPGAFTPTCSSTHvPRYNQLADALKANGVDDIICMSVNDTF-V 83
Cdd:pfam08534   2 AGDKAPDFTLPDaATDGNTVSLSD---FKGKKVVLNFWPGAFCPTCSAEH-PYLEKLNELYKEKGVDVVAVNSDNDAFfV 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 521061791   84 MNEWKaaQEADKITFIPDGNGEFTQGMGLLVDKDqLGFGKRSWRYSMLVKDGVVVKMFIEPEKdgdPFEVSDADTML 160
Cdd:pfam08534  78 KRFWG--KEGLPFPFLSDGNAAFTKALGLPIEED-ASAGLRSPRYAVIDEDGKVVYLFVGPEP---GVDVSDAEAVL 148

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 521061791 173 VTVFTRPGCPFCAKAKGMLKEKGIAFDELVLNKDYRNVTLRAVAGADAVPQVFINGKLIGGSDKLEAWLA 242
Cdd:cd03029    3 VSLFTKPGCPFCARAKAALQENGISYEEIPLGKDITGRSLRAVTGAMTVPQVFIDGELIGGSDDLEKYFA 72

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 521061791 173 VTVFTRPGCPFCAKAKGMLKEKGIAFDELVLNKD--YRNVtLRAVAGADAVPQVFINGKLIGGSDKLEA 239
Cdd:cd02066    2 VVVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDgeLREE-LKELSGWPTVPQIFINGEFIGGYDDLKA 69

Glutaredoxin (GRX) family, GRX bacterial class 1 and 3 (b_1_3)-like subfamily; composed of bacterial 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 E. coli GRX1 and GRX3, which are members of this subfamily.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 521061791 172 DVTVFTRPGCPFCAKAKGMLKEKGIAFDELVLNKD--YRNVTLRAVAGADAVPQVFINGKLIGGSDKLEA 239
Cdd:cd03418    1 KVEIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDpaLREEMINRSGGRRTVPQIFIGDVHIGGCDDLYA 70

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 521061791  173 VTVFTRPGCPFCAKAKGMLKEKGIAFDELVLNKDYRnvtLRAV----AGADAVPQVFINGKLIGGSDKLEA 239
Cdd:TIGR02181   1 VTIYTKPYCPYCTRAKALLSSKGVTFTEIRVDGDPA---LRDEmmqrSGRRTVPQIFIGDVHVGGCDDLYA 68

glutaredoxin 3; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 521061791 172 DVTVFTRPGCPFCAKAKGMLKEKGIAFDELVLNKDY-RNVTLRAVAGADAVPQVFINGKLIGGSDKLEA 239
Cdd:PRK10638   3 NVEIYTKATCPFCHRAKALLNSKGVSFQEIPIDGDAaKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYA 71

Glutaredoxin-like protein, YruB-family; This glutaredoxin-like protein family contains the conserved CxxC motif and includes the Clostridium pasteurianum protein YruB which has been cloned from a rubredoxin operon. Somewhat related to NrdH, it is unknown whether this protein actually interacts with glutathione/glutathione reducatase, or, like NrdH, some other reductant system.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 521061791  173 VTVFTRPGCPFCAKAKGMLKEKGIAFDELVLNKDY--RNVTLRaVAGADAVPQVFINGKLIGGSDK 236
Cdd:TIGR02196   2 VKVYTTPWCPPCVKAKEYLTSKGVAFEEIDVEKDAaaREELLK-VYGQRGVPVIVIGHKIVVGFDP 66

glutaredoxin 1; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 521061791 173 VTVFTRPGCPFCAKAKGM---LKEKGIAFdelvlnkDYRNVTLRA--VAGAD----------AVPQVFINGKLIGGSDKL 237
Cdd:PRK11200   3 VVIFGRPGCPYCVRAKELaekLSEERDDF-------DYRYVDIHAegISKADlektvgkpveTVPQIFVDQKHIGGCTDF 75

                 ....*..
gi 521061791 238 EAWLASN 244
Cdd:PRK11200  76 EAYVKEN 82

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
                 ....*....|....*....|....*...
gi 521061791 173 VTVFTRPGCPFCAKAKGMLKEKGIAFDE 200
Cdd:NF041212   1 VVIYTKPGCPYCAAAKEDLARRGIPFEE 28

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 521061791   7 GKPVPNVTFHTRQDNAWVDVSTEQlFKGKTVVVFSLPGAFTPTCsSTHVPRYNQLADALKANGVdDIICMSVNDTFVMNE 86
Cdd:COG0450    6 GDKAPDFTAEATHGGEFKKISLSD-YKGKWVVLFFHPADFTFVC-PTELGAFAKRYEEFKKLGV-EVIGLSVDSVFSHKA 82

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 521061791  87 WKAAQEAD----KITF--IPDGNGEFTQGMGLLVDKD 117
Cdd:COG0450   83 WHETIKEKggivKIKFpiIADPTGKIARAYGMLHPED 119

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 521061791  176 FTRPGCPFCAKAKGMLKEKGIAFDELVLNKDYRNVTLRAVAGADAVPQVFINGKLIGGSDKLEAWLASN 244
Cdd:pfam13417   2 YGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEEL 70

Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of PICOT and GRX-PICOT-like proteins. The non-PICOT members of this family contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contain three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity. Characterized non-PICOT members of this family include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 521061791 178 RPGCPFCAKAKGMLKEKGI---AFDelVL-NKDYRNvTLRAVAGADAVPQVFINGKLIGGSDKL 237
Cdd:cd03028   20 EPRCGFSRKVVQILNQLGVdfgTFD--ILeDEEVRQ-GLKEYSNWPTFPQLYVNGELVGGCDIV 80

Glutaredoxin-like domain (DUF836); These proteins are related to the pfam00462 family. This entry includes several viral glutaredoxins and many related bacterial and eukaryotic proteins of unknown function. The best characterized member is G4L from Vaccinia virus (strain Western Reserve/WR) (VACV), which is necessary for virion morphogenesis and replication. This is a cytoplasmic protein which functions as a shuttle in a redox pathway between membrane-associated E10R and L1R or F9L.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 521061791  173 VTVFTRPGCPFCAKAKGMLKEKGIAFDELVLNKD-YRNVTLRAVAGaDAVPQVFINGKLIGGS----------DKLEAWL 241
Cdd:pfam05768   1 LTLYGKPGCGLCEGAEEVLEPLALELGFELEVIDiDGDPELLAKYG-LEIPVLAFVGISKFFNleilswrldeEQLAAEL 79

                  .
gi 521061791  242 A 242
Cdd:pfam05768  80 E 80

Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 521061791  181 CPFCAKAKGMLKEKGIAFDELVLNKDYRN--VTLRAVAGADAVPQ-VFINGKLIGGSDKLEAWLAS 243
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELVDLDPKDkpPELLALNPLGTVPVlVLPDGTVLTDSLVILEYLEE 67

GST_N family, Glutaredoxin 2 (GRX2) subfamily; composed of bacterial proteins similar to E. coli GRX2, an atypical GRX with a molecular mass of about 24kD, compared with other GRXs which are 9-12kD in size. GRX2 adopts a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. It contains a redox active CXXC motif located in the N-terminal domain but is not able to reduce ribonucleotide reductase like other GRXs. However, it catalyzes GSH-dependent protein disulfide reduction of other substrates efficiently. GRX2 is thought to function primarily in catalyzing the reversible glutathionylation of proteins in cellular redox regulation including stress responses.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 521061791 181 CPFCAKAKGMLKEKGIAFDELVLNKDYRNVTLRAVaGADAVP 222
Cdd:cd03037    9 CPFCVKARMIAGLKNIPVEQIILQNDDEATPIRMI-GAKQVP 49

Thioredoxin (TRX)-Glutaredoxin (GRX)-like family; composed of archaeal and bacterial proteins that show similarity to both TRX and GRX, including the C-terminal TRX-fold subdomain of Pyrococcus furiosus protein disulfide oxidoreductase (PfPDO). All members contain a redox-active CXXC motif and may function as PDOs. The archaeal proteins Mj0307 and Mt807 show structures more similar to GRX, but activities more similar to TRX. Some members of the family are similar to PfPDO in that they contain a second CXXC motif located in a second TRX-fold subdomain at the N-terminus; the superimposable N- and C-terminal TRX subdomains form a compact structure. PfPDO is postulated to be the archaeal counterpart of bacterial DsbA and eukaryotic protein disulfide isomerase (PDI). The C-terminal CXXC motif of PfPDO is required for its oxidase, reductase and isomerase activities. Also included in the family is the C-terminal TRX-fold subdomain of the N-terminal domain (NTD) of bacterial AhpF, which has a similar fold as PfPDO with two TRX-fold subdomains but without the second CXXC motif.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 521061791 172 DVTVFTRPGCPFCAKAKGMLKEkgIAfdelVLNKdyrNVTLRAVAGAD-----------AVPQVFINGKLIG 232
Cdd:cd02973    2 NIEVFVSPTCPYCPDAVQAANR--IA----ALNP---NISAEMIDAAEfpdladeygvmSVPAIVINGKVEF 64

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
                 ....*....|....*....|....*....|....*...
gi 521061791 149 DPFEVSDADTMLNYIAPNAKKPldVTVFTRPGCPFCAK 186
Cdd:cd03020   59 IDLSALPLDDAIVYGKGNGKRV--VYVFTDPDCPYCRK 94