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 349791342  62 LTFYTHPMSRGRIARWMLEETGLPYETVLLEYG-TSMKAPEYRAINPMGKVPALKHGDVVVTETAAICMYLADL 134
Cdd:cd03046    1 ITLYHLPRSRSFRILWLLEELGLPYELVLYDRGpGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEK 74

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 349791342   60 MKLTFYTHPMS-RGRIARWMLEETGLPYETVLLEYGTS-MKAPEYRAINPMGKVPALKHGDVVVTETAAICMYLAD 133
Cdd:pfam02798   1 MVLTLYGIRGSpRAHRIRWLLAEKGVEYEIVPLDFGAGpEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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 349791342  62 LTFYTHPMSRGRIARWMLEETGLPYETVLLEYG-TSMKAPEYRAINPMGKVPALKHGDVVVTETAAICMYLADL 134
Cdd:cd03046    1 ITLYHLPRSRSFRILWLLEELGLPYELVLYDRGpGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEK 74

Glutathione S-transferase (GST) family, N-terminal 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 subfamily, a member of the DsbA family). 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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, metaxin 2 and stringent starvation protein A.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 349791342  62 LTFYTHPMS-RGRIARWMLEETGLPYETVLLEYGTSmKAPEYRAINPMGKVPALKHGDVVVTETAAICMYLA 132
Cdd:cd00570    1 LKLYYFPGSpRSLRVRLALEEKGLPYELVPVDLGEG-EQEEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 349791342  79 LEETGLPY--ETVLLEYGTSMKAPEYRAINPMGKVPALKHGD-VVVTETAAICMYLADLVPEKKLAPPVGSPERGAYYRW 155
Cdd:PRK10542  18 LRESGLDFtlVSVDLAKKRLENGDDYLAINPKGQVPALLLDDgTLLTEGVAIMQYLADSVPDRQLLAPVGSLSRYHTIEW 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 349791342 156 ISFMAPleqlMIAKtSGAPL--PKSENAGFGTEADLLDT----LEAALTDREYLAGDTFTAADLLVAAYVGWYVQFKL-L 228
Cdd:PRK10542  98 LNYIAT----ELHK-GFTPLfrPDTPEEYKPTVRAQLEKkfqyVDEALADEQWICGQRFTIADAYLFTVLRWAYAVKLnL 172

                        170       180
                 ....*....|....*....|....*.
gi 349791342 229 EPRPAFVQFAERHRKRP---AALRAD 251
Cdd:PRK10542 173 EGLEHIAAYMQRVAERPavaAALKAE 198

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 349791342   60 MKLTFYTHPMS-RGRIARWMLEETGLPYETVLLEYGTS-MKAPEYRAINPMGKVPALKHGDVVVTETAAICMYLAD 133
Cdd:pfam02798   1 MVLTLYGIRGSpRAHRIRWLLAEKGVEYEIVPLDFGAGpEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

GST_N family, unknown subfamily 4; 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 349791342  60 MKLtfYTHPMS-RGRIARWMLEETGLPYETVLLEY-GTSMKAPEYRAINPMGKVPALKHGDVVVTETAAICMYLA 132
Cdd:cd03056    1 MKL--YGFPLSgNCYKVRLLLALLGIPYEWVEVDIlKGETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYLA 73

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 349791342  61 KLTFYTHPMSRG-RIARWMLEETGLPYETVLLE-YGTSMKAPEYRAINPMGKVPALKHGDVVVTETAAICMYLAD 133
Cdd:cd03053    1 VLKLYGAAMSTCvRRVLLCLEEKGVDYELVPVDlTKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAE 75

GST_N family, unknown subfamily 1; composed of uncharacterized proteins, predominantly from bacteria, 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 349791342  77 W-MLEETGLPYETVLLEYGTSMKAPEYRAINPMGKVPALKHGDVVVTETAAICMYLA 132
Cdd:cd03043   17 WlLLKAAGIPFEEILVPLYTPDTRARILEFSPTGKVPVLVDGGIVVWDSLAICEYLA 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 349791342  60 MKLTFYTHpmsRGR--IARWMLEETGLPYETVLLEYGTSMKApEYRAINPMGKVPALKHGDVVVTETAAICMYLAD 133
Cdd:cd03039    1 YKLTYFNI---RGRgePIRLLLADAGVEYEDVRITYEEWPEL-DLKPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 349791342  79 LEETGLPYETVLLEY-GTSMKAPEYRAINPMGKVPALKHGDVVVTETAAICMYLADLVPEKK---LAPPVgsPERGAYYR 154
Cdd:PLN02395  20 LIEKGVEFETVPVDLmKGEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYRSQGpdlLGKTI--EERGQVEQ 97

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 349791342 155 WI-----SFMAPLEQL----MIAKTSGAP-----LPKSENagfgTEADLLDTLEAALTDREYLAGDTFTAADL 213
Cdd:PLN02395  98 WLdveatSYHPPLLNLtlhiLFASKMGFPadekvIKESEE----KLAKVLDVYEARLSKSKYLAGDFVSLADL 166

C-terminal, alpha helical domain of Class Beta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Beta 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. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they are involved in the protection against oxidative stress and are able to bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs, contributing to antibiotic resistance. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH. One member of this subfamily is a GST from Burkholderia xenovorans LB400 that is encoded by the bphK gene and is part of the biphenyl catabolic pathway.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 349791342 187 ADLLDTLEAALTDREYLAGDTFTAADLLVAAYVGWYVQFKL-LEPRPAFVQFAERHRKRPAALRA 250
Cdd:cd03188   48 ERRLAYLDAQLAGGPYLLGDQFSVADAYLFVVLRWARAVGLdLSDWPHLAAYLARVAARPAVQAA 112

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 349791342  79 LEETGLPYETVLLEYGTSmkaPE-YRAINPMGKVPALKHGDVVVTETAAICMYLADLVPEKKLAPPvgsPERGA-----Y 152
Cdd:PLN02817  83 LEEKHLPYDMKLVDLTNK---PEwFLKISPEGKVPVVKLDEKWVADSDVITQALEEKYPDPPLATP---PEKASvgskiF 156

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 349791342 153 YRWISFMapleqlmiaktsgaplpKSENAGFGTEADLLDTLeAALTDR-----EYLAGDTFTAADLLVA 216
Cdd:PLN02817 157 STFIGFL-----------------KSKDPGDGTEQALLDEL-TSFDDYikengPFINGEKISAADLSLG 207

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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 349791342  83 GLPYETVLLEYGTSMKAPEYRAINPMGKVPALKHGD-VVVTETAAICMYLADL 134
Cdd:cd03044   23 GLDVEIVDFQPGKENKTPEFLKKFPLGKVPAFEGADgFCLFESNAIAYYVANL 75

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 349791342  62 LTFYTHPMSRGRIARWMLEETGLPYETVLLEYGTSMK-APEYRAINPMGKVPAL-KHG------DVVVTETAAICMYLAD 133
Cdd:PRK13972   2 IDLYFAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQfRPEFLRISPNNKIPAIvDHSpadggePLSLFESGAILLYLAE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 349791342 134 lvpEKKLAPPVGSPERGAYYRWISFMAPLEQLMIAKTSGAPLPKSENAGFGTEADLLDT------LEAALTDREYLAGDT 207
Cdd:PRK13972  82 ---KTGLFLSHETRERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETqrlyhvLNKRLENSPWLGGEN 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 349791342 208 FTAADLLVAAYV-GWYVQFKLLEPRPAFVQFAERHRKRPAA----LRADEIDE 255
Cdd:PRK13972 159 YSIADIACWPWVnAWTRQRIDLAMYPAVKNWHERIRSRPATgqalLKAQLGDE 211

C-terminal, alpha helical domain of Ure2p and related Glutathione S-transferase-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p, YfcG and YghU from Escherichia coli, and related GST-like proteins. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The N-terminal thioredoxin-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. YfcG and YghU are two of the nine GST homologs in the genome of Escherichia coli. They display very low or no GSH transferase, but show very good disulfide bond oxidoreductase activity. YghU also shows modest organic hydroperoxide reductase activity. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 349791342 189 LLDTLEAALTDREYLAGDTFTAADLlvaAYVGWYVQFKL-----LEPRPAFVQFAERHRKRPA 246
Cdd:cd03178   48 LYGVLDKRLSDRPYLAGEEYSIADI---ALYPWTHYADLggfadLSEYPNVKRWLERIAARPA 107

glutathione S-transferase DHAR1

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 349791342  79 LEETGLPYETVLLEYgtSMKAPEYRAINPMGKVPALKHGDVVVTETAAICMYLADLVPEKKLAPPVGSPERGAYyrwisf 158
Cdd:PLN02378  30 LEEKSLTYKIHLINL--SDKPQWFLDISPQGKVPVLKIDDKWVTDSDVIVGILEEKYPDPPLKTPAEFASVGSN------ 101

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 349791342 159 mapleqlmIAKTSGAPLpKSENAGFGTEADLLDTLEAALT-----DREYLAGDTFTAADLLVA 216
Cdd:PLN02378 102 --------IFGTFGTFL-KSKDSNDGSEHALLVELEALENhlkshDGPFIAGERVSAVDLSLA 155

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 349791342  75 ARWMLEETGLPYEtvLLEYGTSMKAPEYRAINPM-GKVPALKHGDVVVTETAAICMYLAD 133
Cdd:cd03058   15 VRIALALKGVPYE--YVEEDLGNKSELLLASNPVhKKIPVLLHNGKPICESLIIVEYIDE 72

C-terminal, alpha helical domain of GTT2-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the Saccharomyces 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 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. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 349791342 187 ADLLDTLEAALTDREYLAGDTFTAADLLVAAYVGWYVQFKLLEP--RPAFVQFAERHRKRPAA 247
Cdd:cd03182   54 IDFLPVLDKRLAESPYVAGDRFSIADITAFVALDFAKNLKLPVPeeLTALRRWYERMAARPSA 116

C-terminal, alpha helical domain of Escherichia coli Yghu Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YghU-like subfamily; composed of the Escherichia coli YghU 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. YghU is one of nine GST homologs in the genome of Escherichia coli. It is similar to Escherichia coli YfcG in that it has poor GSH transferase activity towards typical substrates. It shows modest reductase activity towards some organic hydroperoxides. Like YfcG, YghU also shows good disulfide bond oxidoreductase activity comparable to the activities of glutaredoxins and thioredoxins. YghU 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 YghU reveals two GSH molecules bound in its active site.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 349791342 183 FGTEAD-LLDTLEAALTDREYLAGDTFTAADLLVAAYVGWYVQFKL--------LEPRPAFVQFAERHRKRPAALR 249
Cdd:cd10292   41 FTMEAKrQLDVLDRQLATHKYLAGDEYTIADMAIWPWYGGLALGSLydaaefldVDEYKHVQRWAKDIAARPAVKR 116

C-terminal, alpha helical domain of an unknown subfamily 2 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 349791342 187 ADLLDTLEAALTDREYLAGDTFTAADLLVAAYV-GWY-----------VQ--FKLLEPRPAF 234
Cdd:cd03180   49 NKLMAILDAQLARQAYLAGDRFTLADIALGCSVyRWLelpierpalphLErwYARLSQRPAF 110

C-terminal, alpha helical domain of Class Delta and Epsilon Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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.

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gi 349791342 190 LDTLEAALTDREYLAGDTFTAADLLVAAYVGWYVQFKL-LEPRPAFVQFAER 240
Cdd:cd03177   47 LEFLETFLEGSDYVAGDQLTIADLSLVATVSTLEVVGFdLSKYPNVAAWYER 98

GST_N family, Class Mu 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 class Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1), thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

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gi 349791342  76 RWMLEETGLPYETVLLEYGtsmKAPEY------RAINPMGK----VPALKHGDVVVTETAAICMYLAD 133
Cdd:cd03075   16 RLLLEYTGEKYEEKRYELG---DAPDYdrsqwlNEKFKLGLdfpnLPYYIDGDVKLTQSNAILRYIAR 80

GST_N family, Class Omega 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 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. They 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. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

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gi 349791342  75 ARWMLEETGLPYETVLLEYGTSmkaPE-YRAINPMGKVPALKH-GDVVVTETAAICMYL 131
Cdd:cd03055   33 ARLVLAAKNIPHEVININLKDK---PDwFLEKNPQGKVPALEIdEGKVVYESLIICEYL 88

C-terminal, alpha helical domain of Class Omega-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae Omega-like subfamily; composed of three Saccharomyces cerevisiae GST omega-like (Gto) proteins, Gto1p, Gto2p (also known as Extracellular mutant protein 4 or ECM4p), and Gto3p, as well as similar uncharacterized proteins from fungi and bacteria. The three Saccharomyces cerevisiae Gto proteins are omega-class GSTs with low or no GST activity against standard substrates, but have glutaredoxin/thiol oxidoreductase and dehydroascorbate reductase activity through a single cysteine residue in the active site. Gto1p is located in the peroxisomes while Gto2p and Gto3p are cytosolic. The gene encoding Gto2p, called ECM4, is involved in cell surface biosynthesis and architecture. S. cerevisiae ECM4 mutants show increased amounts of the cell wall hexose, N-acetylglucosamine. More recently, global gene expression analysis shows that ECM4 is upregulated during genotoxic conditions and together with the expression profiles of 18 other genes could potentially differentiate between genotoxic and cytotoxic insults in yeast.

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gi 349791342 190 LDTLEAALTDREYLAGDTFTAADL 213
Cdd:cd03190   46 LDKLEKRLSKQPYLLGDRLTEADI 69