C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Zeta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Class Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor. They show little GSH-conjugating activity towards traditional GST substrates, but display modest GSH peroxidase activity. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671  93 PKKRASVRMISDLIAGGIQPLQNLSVLKQVG------EEMQLTWAQNAITCGFNALEQILQSTAGIYCVGDEVTMADLCL 166
Cdd:cd03191    1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTeklgvsEEEKLAWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 269849671 167 VPQVANAERFKVDLTPYPTISSINKRLLVLEAFQVSHPCRQ 207
Cdd:cd03191   81 VPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671   1 MQAGKPILYS--YFRSSCSWRVRIALALKGIDYKTVPINLikDRGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEY 78
Cdd:PRK15113   1 MSKPAITLYSdaHFFSPYVMSAFVALQEKGLPFELKTVDL--DAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEY 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 269849671  79 LEEMRPTP---RLLPQDPKKRASVRMI-----SDLIA 107
Cdd:PRK15113  79 LEERFAPPaweRIYPADLQARARARQIqawlrSDLMP 115

C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Zeta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Class Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor. They show little GSH-conjugating activity towards traditional GST substrates, but display modest GSH peroxidase activity. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671  93 PKKRASVRMISDLIAGGIQPLQNLSVLKQVG------EEMQLTWAQNAITCGFNALEQILQSTAGIYCVGDEVTMADLCL 166
Cdd:cd03191    1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTeklgvsEEEKLAWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 269849671 167 VPQVANAERFKVDLTPYPTISSINKRLLVLEAFQVSHPCRQ 207
Cdd:cd03191   81 VPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

GST_N family, Class Zeta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor. They show little GSH-conjugating activity towards traditional GST substrates but display modest GSH peroxidase activity. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 269849671   6 PILYSYFRSSCSWRVRIALALKGIDYKTVPINLIKdrGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLE 80
Cdd:cd03042    1 MILYSYFRSSASYRVRIALNLKGLDYEYVPVNLLK--GEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYLD 73

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671   1 MQAGKPILYS--YFRSSCSWRVRIALALKGIDYKTVPINLikDRGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEY 78
Cdd:PRK15113   1 MSKPAITLYSdaHFFSPYVMSAFVALQEKGLPFELKTVDL--DAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEY 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 269849671  79 LEEMRPTP---RLLPQDPKKRASVRMI-----SDLIA 107
Cdd:PRK15113  79 LEERFAPPaweRIYPADLQARARARQIqawlrSDLMP 115

Glutathione S-transferase, N-terminal domain; Function: conjugation of reduced glutathione to a variety of targets. Also included in the alignment, but not GSTs: S-crystallins from squid (similarity to GST previously noted); eukaryotic elongation factors 1-gamma (not known to have GST activity and similarity not previously recognized); HSP26 family of stress-related proteins including auxin-regulated proteins in plants and stringent starvation proteins in E. coli (not known to have GST activity and similarity not previously recognized). The glutathione molecule binds in a cleft between the N- and C-terminal domains - the catalytically important residues are proposed to reside in the N-terminal domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 269849671    7 ILYSYFRSSCSWRVRIALALKGIDYKTVPINLikDRGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEE 81
Cdd:pfam02798   4 TLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDF--GAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

GST_N family, Class Phi subfamily; composed of plant-specific class Phi GSTs and related fungal and bacterial proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Phi GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Tau GSTs, showing class specificity in substrate preference. Phi enzymes are highly reactive toward chloroacetanilide and thiocarbamate herbicides. Some Phi GSTs have other functions including transport of flavonoid pigments to the vacuole, shoot regeneration and GSH peroxidase activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 269849671   5 KPILYSYFRSSCSWRVRIALALKGIDYKTVPINLIKdrGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEE 81
Cdd:cd03053    1 VLKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTK--GEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAE 75

GST_N family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT2. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GTT2, a homodimer, exhibits GST activity with standard substrates. Strains with deleted GTT2 genes are viable but exhibit increased sensitivity to heat shock.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 269849671   8 LYSYFRSSCSWRVRIALALKGIDYKTVPINLIKdrGQQFSKDFQALNPMKQVPTLKI-DGITIHQSLAIIEYLE 80
Cdd:cd03051    3 LYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAA--GEQRSPEFLAKNPAGTVPVLELdDGTVITESVAICRYLE 74

GST_N family, Saccharomyces cerevisiae GTT1-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT1, and the Schizosaccharomyces pombe GST-III. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GTT1, a homodimer, exhibits GST activity with standard substrates and associates with the endoplasmic reticulum. Its expression is induced after diauxic shift and remains high throughout the stationary phase. S. pombe GST-III is implicated in the detoxification of various metals.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 269849671   6 PILYsYFRSSCSWRVRIALALKGIDYKTVPINLikDRGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEE 81
Cdd:cd03046    1 ITLY-HLPRSRSFRILWLLEELGLPYELVLYDR--GPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAE 73

GST_N family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi and Alpha. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation and mediation of allergy and inflammation. Other class Sigma members include the class II insect GSTs, S-crystallins from cephalopods and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase and PGD2 synthase activities, and may play an important role in host-parasite interactions. Also members are novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671  20 VRIALALKGIDYKTVPInlikDRGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYL 79
Cdd:cd03039   15 IRLLLADAGVEYEDVRI----TYEEWPELDLKPTLPFGQLPVLEIDGKKLTQSNAILRYL 70

GST_N family, Class Delta and Epsilon subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Delta and Epsilon subfamily is made up primarily of insect GSTs, which play major roles in insecticide resistance by facilitating reductive dehydrochlorination of insecticides or conjugating them with GSH to produce water-soluble metabolites that are easily excreted. They are also implicated in protection against cellular damage by oxidative stress.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 269849671   6 PILYSYFRSSCSWRVRIALALKGIDYKTVPINLIKdrGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEE 81
Cdd:cd03045    1 IDLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMK--GEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

GST_N family, Class Tau subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 269849671   7 ILYSYFRSSCSWRVRIALALKGIDYKTVPINLIKDrgqqfSKDFQALNPM-KQVPTLKIDGITIHQSLAIIEYLEE 81
Cdd:cd03058    2 KLLGAWASPFVLRVRIALALKGVPYEYVEEDLGNK-----SELLLASNPVhKKIPVLLHNGKPICESLIIVEYIDE 72

GST_N family, Beta etherase LigE subfamily; composed of proteins similar to Sphingomonas paucimobilis beta etherase, LigE, a GST-like protein that catalyzes the cleavage of the beta-aryl ether linkages present in low-moleculer weight lignins using GSH as the hydrogen donor. This reaction is an essential step in the degradation of lignin, a complex phenolic polymer that is the most abundant aromatic material in the biosphere. The beta etherase activity of LigE is enantioselective and it complements the activity of the other GST family beta etherase, LigF.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 269849671  18 WRVRIALALKGIDYKTVPINLIKDRGQQFSKDfqaLNPMKQVPTLK-IDGITIHQSLAIIEYLEEMRP 84
Cdd:cd03038   20 WKTRLALNHKGLEYKTVPVEFPDIPPILGELT---SGGFYTVPVIVdGSGEVIGDSFAIAEYLEEAYP 84

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 269849671   8 LYSYFRSSCSWRVRIALALKGIDYKTVPINLikdrgQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEE 81
Cdd:cd03059    3 LYSGPDDVYSHRVRIVLAEKGVSVEIIDVDP-----DNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDE 71

putative glutathione S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671  53 LNPMKQVPTLKID-GITIHQSLAIIEYLEEMRPTPRLLPQDPKKRASVRMISDLiAGGIQPLQNLSVLKQV-----GEEM 126
Cdd:PRK10357  43 YNPLGKVPALVTEeGECWFDSPIIAEYIELLNVAPAMLPRDPLAALRVRQLEAL-ADGIMDAALVSVREQArpaaqQSED 121

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 269849671 127 QLTWAQNAITCGFNALEQILQS-TAGiycvGDEVTMADL 164
Cdd:PRK10357 122 ELLRQREKINRSLDALEGYLVDgTLK----TDTVNLATI 156

C-terminal, alpha helical domain of the Glutathione S-transferase family; Glutathione S-transferase (GST) family, C-terminal alpha helical domain; a large, diverse group of cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxins, stringent starvation protein A, and aminoacyl-tRNA synthetases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671  96 RASVRMISDLIAGGIQPLQNLSVLKQVGEEMQLTWAQNAITCGFNALEQILQSTAgiYCVGDEVTMADLCLVPQVANAER 175
Cdd:cd00299    2 RALEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRP--YLAGDQFSLADVALAPVLARLEA 79

                         90       100
                 ....*....|....*....|.
gi 269849671 176 FKV---DLTPYPTISSINKRL 193
Cdd:cd00299   80 LGPyydLLDEYPRLKAWYDRL 100

GST_N family, Gamma subunit of Elongation Factor 1B (EFB1gamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal TRX-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 269849671   8 LYSYFRSSCSWRVRIALALKGIDYKTVPINLIKDrgqQFSKDFQALNPMKQVPTLKI-DGITIHQSLAIIEYL 79
Cdd:cd03044    3 LYTYPGNPRSLKILAAAKYNGLDVEIVDFQPGKE---NKTPEFLKKFPLGKVPAFEGaDGFCLFESNAIAYYV 72

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671  19 RVRIALALKGIDYKTVPINLikDRGQQFSKDFQALNPMKQVPTL----KIDG---ITIHQSLAIIEYLEEmrPTPRLLPQ 91
Cdd:PRK13972  14 KITLFLEEAELDYRLIKVDL--GKGGQFRPEFLRISPNNKIPAIvdhsPADGgepLSLFESGAILLYLAE--KTGLFLSH 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671  92 DPKKRASVRMISDLIAGGIQPL--QNLSVLKQVGEEMQLTWAQNAITCG--FNALEQILQSTAgiYCVGDEVTMADLCLV 167
Cdd:PRK13972  90 ETRERAATLQWLFWQVGGLGPMlgQNHHFNHAAPQTIPYAIERYQVETQrlYHVLNKRLENSP--WLGGENYSIADIACW 167

                        170       180
                 ....*....|....*....|....*.
gi 269849671 168 PQVANAERFKVDLTPYPTISSINKRL 193
Cdd:PRK13972 168 PWVNAWTRQRIDLAMYPAVKNWHERI 193

glutathione s-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671   7 ILYSYFRSSCSWRVRIALALKGIDYKTVPINLIKDRGQQFsKDF--QALNPMKQVPTLKIDGITIHQSLAIIEYLEEMRP 84
Cdd:PTZ00057   6 VLYYFDARGKAELIRLIFAYLGIEYTDKRFGENGDAFIEF-KNFkkEKDTPFEQVPILEMDNIIFAQSQAIVRYLSKKYK 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849671  85 TprllpqdPKKRASVRMISDLIAGGIQPLQ----NLSVLKQvgeeMQLTWAQNAITCGFNALEQILQSTAGIYCVGDEVT 160
Cdd:PTZ00057  85 I-------CGESELNEFYADMIFCGVQDIHykfnNTNLFKQ----NETTFLNEELPKWSGYFENILKKNHCNYFVGDNLT 153

                        170       180       190
                 ....*....|....*....|....*....|..
gi 269849671 161 MADLCLVPQVANAE-RFKVDLTPYPTISSINK 191
Cdd:PTZ00057 154 YADLAVFNLYDDIEtKYPNSLKNFPLLKAHNE 185

NrdH-redoxin (NrdH) family; NrdH is a small monomeric protein with a conserved redox active CXXC motif within a TRX fold, characterized by a glutaredoxin (GRX)-like sequence and TRX-like activity profile. In vitro, it displays protein disulfide reductase activity that is dependent on TRX reductase, not glutathione (GSH). It is part of the NrdHIEF operon, where NrdEF codes for class Ib ribonucleotide reductase (RNR-Ib), an efficient enzyme at low oxygen levels. Under these conditions when GSH is mostly conjugated to spermidine, NrdH can still function and act as a hydrogen donor for RNR-Ib. It has been suggested that the NrdHEF system may be the oldest RNR reducing system, capable of functioning in a microaerophilic environment, where GSH was not yet available. NrdH from Corynebacterium ammoniagenes can form domain-swapped dimers, although it is unknown if this happens in vivo. Domain-swapped dimerization, which results in the blocking of the TRX reductase binding site, could be a mechanism for regulating the oxidation state of the protein.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 269849671   7 ILYSyfRSSCSW--RVRIALALKGIDYKTVPInlikDRGQQFSKDFQALNPMKQVPTLKIDG 66
Cdd:cd02976    3 TVYT--KPDCPYckATKRFLDERGIPFEEVDV----DEDPEALEELKKLNGYRSVPVVVIGD 58

C-terminal, alpha helical domain of Escherichia coli YfcG Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YfcG-like subfamily; composed of the Escherichia coli YfcG and related proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YfcG is one of nine GST homologs in Escherichia coli. It is expressed predominantly during the late stationary phase where the predominant form of GSH is glutathionylspermidine (GspSH), suggesting that YfcG might interact with GspSH. It has very low or no GSH transferase or peroxidase activity, but displays a unique disulfide bond reductase activity that is comparable to thioredoxins (TRXs) and glutaredoxins (GRXs). However, unlike TRXs and GRXs, YfcG does not contain a redox active cysteine residue and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YcfG reveals a bound GSSG molecule in its active site. The actual physiological substrates for YfcG are yet to be identified.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 269849671 142 LEQILQSTAgiYCVGDEVTMADLCLVPQVANAERFKVDLTPYPTISSINKRLLVLEAFQ 200
Cdd:cd10291   52 LDRRLAKSK--YLAGDEYSIADIAIWPWVARHEWQGIDLADFPNLKRWFERLAARPAVQ 108

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 269849671  11 YFRSSCSW--RVRIALALKGIDYKTVPInlikDRGQQFSKDFQALNPMKQVPTLKIDG--ITIHQSLAIIEYLE 80
Cdd:COG0695    5 YTTPGCPYcaRAKRLLDEKGIPYEEIDV----DEDPEAREELRERSGRRTVPVIFIGGehLGGFDEGELDALLA 74

GST_N family, Omega-like subfamily; composed of uncharacterized proteins with similarity to class Omega GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. Like Omega enzymes, proteins in this subfamily contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 269849671   6 PILYSYFRSSCSWRVRIALALKGIDYKTVPINLiKDRgqqfSKDFQALNPMKQVPTL-KIDGITIHQSLAII 76
Cdd:cd03060    1 PILYSFRRCPYAMRARMALLLAGITVELREVEL-KNK----PAEMLAASPKGTVPVLvLGNGTVIEESLDIM 67

GST_N family, unknown subfamily 2; composed of uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The sequence from Burkholderia cepacia was identified as part of a gene cluster involved in the degradation of 2,4,5-trichlorophenoxyacetic acid. Some GSTs (e.g. Class Zeta and Delta) are known to catalyze dechlorination reactions.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 269849671  41 DRGQQFSK----DFQALNPMKQVPTLKIDGITIHQSLAIIEYL 79
Cdd:cd03047   30 DAGGQFGGldtpEFLAMNPNGRVPVLEDGDFVLWESNAILRYL 72