Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465   1 MITVWGRENSTNVKKVLWCLEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRDDetGLVLWESNAIVRYLAAQYG 80
Cdd:COG0625    1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDD--GLVLTESLAILEYLAERYP 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465  81 QGRLWLESPVERARGEKWMDWAISTLPAPHRGVVFSLVrtppEQRDPALIEESKKQCDALFGILDAELAKTPWLSGDAFG 160
Cdd:COG0625   79 EPPLLPADPAARARVRQWLAWADGDLHPALRNLLERLA----PEKDPAAIARARAELARLLAVLEARLAGGPYLAGDRFS 154

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 696410465 161 IADMAPAPHIYNLFNVGIEWTPRPHLERWYQQLTERPAFR 200
Cdd:COG0625  155 IADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAFQ 194

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465   1 MITVWGRENSTNVKKVLWCLEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRDDetGLVLWESNAIVRYLAAQYG 80
Cdd:COG0625    1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDD--GLVLTESLAILEYLAERYP 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465  81 QGRLWLESPVERARGEKWMDWAISTLPAPHRGVVFSLVrtppEQRDPALIEESKKQCDALFGILDAELAKTPWLSGDAFG 160
Cdd:COG0625   79 EPPLLPADPAARARVRQWLAWADGDLHPALRNLLERLA----PEKDPAAIARARAELARLLAVLEARLAGGPYLAGDRFS 154

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 696410465 161 IADMAPAPHIYNLFNVGIEWTPRPHLERWYQQLTERPAFR 200
Cdd:COG0625  155 IADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAFQ 194

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465  14 KKVLWCLEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRDDEtgLVLWESNAIVRYLAAQY-GQGRLWLESPVE- 91
Cdd:PLN02395  14 KRALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGD--YKIFESRAIMRYYAEKYrSQGPDLLGKTIEe 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465  92 RARGEKWMDWAISTLPAPHRG----VVFSLVRTPPEqrDPALIEESKKQCDALFGILDAELAKTPWLSGDAFGIADMAPA 167
Cdd:PLN02395  92 RGQVEQWLDVEATSYHPPLLNltlhILFASKMGFPA--DEKVIKESEEKLAKVLDVYEARLSKSKYLAGDFVSLADLAHL 169

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 696410465 168 PHI-YNLFNVGIEW--TPRPHLERWYQQLTERPAFRNIV 203
Cdd:PLN02395 170 PFTeYLVGPIGKAYliKDRKHVSAWWDDISSRPAWKEVL 208

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465   1 MITVWGRENSTNVKKVLWCLEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRDDetGLVLWESNAIVRYLAAQYG 80
Cdd:COG0625    1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDD--GLVLTESLAILEYLAERYP 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465  81 QGRLWLESPVERARGEKWMDWAISTLPAPHRGVVFSLVrtppEQRDPALIEESKKQCDALFGILDAELAKTPWLSGDAFG 160
Cdd:COG0625   79 EPPLLPADPAARARVRQWLAWADGDLHPALRNLLERLA----PEKDPAAIARARAELARLLAVLEARLAGGPYLAGDRFS 154

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 696410465 161 IADMAPAPHIYNLFNVGIEWTPRPHLERWYQQLTERPAFR 200
Cdd:COG0625  155 IADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAFQ 194

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        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 696410465   2 ITVWGRENSTNVKKVLWCLEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRDDEtgLVLWESNAIVRYLA 76
Cdd:cd03047    1 LTIWGRRSSINVQKVLWLLDELGLPYERIDAGGQFGGLDTPEFLAMNPNGRVPVLEDGD--FVLWESNAILRYLA 73

GST_N family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p and related GSTs. 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The N-terminal TRX-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. Characterized GSTs in this subfamily include Aspergillus fumigatus GSTs 1 and 2, and Schizosaccharomyces pombe GST-I. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465   1 MITVWGrENSTNVKKVLWCLEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRD-DETGLVLWESNAIVRYLAAQY 79
Cdd:cd03048    1 MITLYT-HGTPNGFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDhNGTPLTVFESGAILLYLAEKY 79

                 ..
gi 696410465  80 GQ 81
Cdd:cd03048   80 DK 81

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 696410465   2 ITVWGRENSTNVKKVLWCLEELELPYNRIPAGgkYGINHDADYLEMNPNGLVPCLRDDetGLVLWESNAIVRYLA 76
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVD--LGEGEQEEFLALNPLGKVPVLEDG--GLVLTESLAILEYLA 71

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465  42 ADYLEMNPNGLVPCLRDDEtGLVLWESNAIVRYLAAQYGQGRLwLESP--VERARGEKWMDWAISTLpapHRGvvFSLVR 119
Cdd:PRK10542  41 DDYLAINPKGQVPALLLDD-GTLLTEGVAIMQYLADSVPDRQL-LAPVgsLSRYHTIEWLNYIATEL---HKG--FTPLF 113

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465 120 TP--PEQRDPALIEESKKQcdalFGILDAELAKTPWLSGDAFGIADMapaphiYnLFNVgIEWTP--------RPHLERW 189
Cdd:PRK10542 114 RPdtPEEYKPTVRAQLEKK----FQYVDEALADEQWICGQRFTIADA------Y-LFTV-LRWAYavklnlegLEHIAAY 181

                 ....*....
gi 696410465 190 YQQLTERPA 198
Cdd:PRK10542 182 MQRVAERPA 190

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 696410465   2 ITVWGRENSTNVKKVLWCLEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRDDetGLVLWESNAIVRYLAAQ 78
Cdd:cd03053    2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDG--DLKLFESRAITRYLAEK 76

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465  91 ERARGEKWMDWAISTLPAPHRGVVFslvrtPPEQRDPALIEESKKQC----DALFGILDAELAKTPWLSGDAFGIADmap 166
Cdd:cd03188    2 ERARLLEWLNFIASELHKAFGPLFY-----PARWADDALAEEVKAAArerlERRLAYLDAQLAGGPYLLGDQFSVAD--- 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 696410465 167 aphIYnLF-------NVGIEWTPRPHLERWYQQLTERPAFRN 201
Cdd:cd03188   74 ---AY-LFvvlrwarAVGLDLSDWPHLAAYLARVAARPAVQA 111

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 696410465   2 ITVWGRENSTNVKKVLWCLEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRDDetGLVLWESNAIVRYLA 76
Cdd:cd03056    1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLALNPNGEVPVLELD--GRVLAESNAILVYLA 73

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 696410465  98 WMDWAISTLPAPhrGVVFSLVRTPPEQRDPALIEESKKQCDALFGILDAELAKTPWLSGDAFGIADMAPAPHIYNLFNVG 177
Cdd:cd00299    4 LEDWADATLAPP--LVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEALG 81

                         90
                 ....*....|....*....
gi 696410465 178 IE---WTPRPHLERWYQQL 193
Cdd:cd00299   82 PYydlLDEYPRLKAWYDRL 100

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465  91 ERARGEKWMDWAISTLPaPHRGVVFSLVRTPPEqRDPALIEESKKQCDALFGILDAELAKTPWLSGDAFGIADMAPAPHI 170
Cdd:cd03178    1 ERAEVLQWLFFQMSGLG-PMFGQAGHFLYFAPE-KIPYAIERYTDEVKRLYGVLDKRLSDRPYLAGEEYSIADIALYPWT 78

                         90       100       110
                 ....*....|....*....|....*....|
gi 696410465 171 YNLFNVGIEWTPR-PHLERWYQQLTERPAF 199
Cdd:cd03178   79 HYADLGGFADLSEyPNVKRWLERIAARPAV 108

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit limited GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they also bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465  20 LEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRDDEtGLVLWESNAIVRYLAAQY 79
Cdd:cd03057   18 LEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVLDD-GEVLTESAAILQYLADLH 76

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 696410465    6 GRENSTNVKKVLWCLEELELPYNRIPAGGkygINHDADYLEMNPNGLVPCLRDDetGLVLWESNAIVRYLAAQYGQ 81
Cdd:pfam13417   3 GFPGSPYARRVRIALNEKGLPYEFVPIPP---GDHPPELLAKNPLGKVPVLEDD--GGILCESLAIIDYLEELYPG 73

GST_N family, 2 repeats of the N-terminal domain of soluble GSTs (2 GST_N) subfamily; composed of uncharacterized 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 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 696410465   1 MITVWGRENSTNVKKVLWCLEELELPY--NRIPAGGKYginhDADYLEMNPNGLVPCLRDDETGLVLWESNAIVRYLAAQ 78
Cdd:cd03041    1 PLELYEFEGSPFCRLVREVLTELELDVilYPCPKGSPK----RDKFLEKGGKVQVPYLVDPNTGVQMFESADIVKYLFKT 76

                 .
gi 696410465  79 Y 79
Cdd:cd03041   77 Y 77

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 696410465 127 PALIEESKKQCDALFGILDAELAKTPWLSGDAFGIADMapAPHIYNLFNVGIEWTP---RPHLERWYQQLTERPAF 199
Cdd:cd03182   43 PEWGERNKKRVIDFLPVLDKRLAESPYVAGDRFSIADI--TAFVALDFAKNLKLPVpeeLTALRRWYERMAARPSA 116

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 696410465  16 VLWCLEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRDDetGLVLWESNAIVRYLAA 77
Cdd:cd03045   15 VLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDN--GFVLWESHAILIYLVE 74

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 696410465 132 ESKKQCDalfgILDAELAKTPWLSGDAFGIADMAPAPHIYNLFNVG-------IEWTPRPHLERWYQQLTERPA 198
Cdd:cd10292   44 EAKRQLD----VLDRQLATHKYLAGDEYTIADMAIWPWYGGLALGSlydaaefLDVDEYKHVQRWAKDIAARPA 113

GST_N family, Class Theta subfamily; composed of eukaryotic class Theta GSTs and bacterial dichloromethane (DCM) dehalogenase. 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. Mammalian class Theta GSTs show poor GSH conjugating activity towards the standard substrates, CDNB and ethacrynic acid, differentiating them from other mammalian GSTs. GSTT1-1 shows similar cataytic activity as bacterial DCM dehalogenase, catalyzing the GSH-dependent hydrolytic dehalogenation of dihalomethanes. This is an essential process in methylotrophic bacteria to enable them to use chloromethane and DCM as sole carbon and energy sources. The presence of polymorphisms in human GSTT1-1 and its relationship to the onset of diseases including cancer is subject of many studies. Human GSTT2-2 exhibits a highly specific sulfatase activity, catalyzing the cleavage of sulfate ions from aralkyl sufate esters, but not from aryl or alkyl sulfate esters.

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gi 696410465  16 VLWCLEELELPYNRIPAGGKYGINHDADYLEMNPNGLVPCLRDDetGLVLWESNAIVRYLAAQY 79
Cdd:cd03050   15 VYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDG--DFTLAESVAILRYLARKF 76

C-terminal, alpha helical domain of an unknown subfamily 7 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 7; composed of uncharacterized 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.

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gi 696410465 130 IEESKKQCDALFGILDAELAKTPWLSGDAFGIADMAPAPHIYNLFNVGIEWTPRPHLERWYQQLTERPAF 199
Cdd:cd03206   31 PERARAISHRLLRLLDQHLAGRDWLAGDRPTIADVACYPYIALAPEGGVSLEPYPAIRAWLARVEALPGF 100

C-terminal, alpha helical domain of Ganglioside-induced differentiation-associated protein 1; Glutathione S-transferase (GST) C-terminal domain family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) subfamily; GDAP1 was originally identified as a highly expressed gene at the differentiated stage of GD3 synthase-transfected cells. More recently, mutations in GDAP1 have been reported to cause both axonal and demyelinating autosomal-recessive Charcot-Marie-Tooth (CMT) type 4A neuropathy. CMT is characterized by slow and progressive weakness and atrophy of muscles. Sequence analysis of GDAP1 shows similarities and differences with GSTs; it appears to contain both N-terminal thioredoxin-fold and C-terminal alpha helical domains of GSTs, however, it also contains additional C-terminal transmembrane domains unlike GSTs. GDAP1 is mainly expressed in neuronal cells and is localized in the mitochondria through its transmembrane domains. It does not exhibit GST activity using standard substrates.

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gi 696410465 147 ELAKTPWLSGDAFGIADMAPAPHIYNLFNVGI---EW--TPRPHLERWYQQLTERPAF 199
Cdd:cd10303   54 EEGQQPWLCGEFFSLADVSLAVTLHRLKFLGLarrNWgnGKRPNLETYYERVLKRKTF 111

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.

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gi 696410465  40 HDADYLEMNPNGLVPCLRDDetGLVLWESNAIVRYL 75
Cdd:cd03042   39 LSPAYRALNPQGLVPTLVID--GLVLTQSLAIIEYL 72

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.

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gi 696410465   3 TVWGRENSTNVKKVL----WCLEELELPYNriPAGGKygiNHDADYLEMNPNGLVPCLRDDEtGLVLWESNAIVRYLAAQ 78
Cdd:cd03044    2 TLYTYPGNPRSLKILaaakYNGLDVEIVDF--QPGKE---NKTPEFLKKFPLGKVPAFEGAD-GFCLFESNAIAYYVANL 75

C-terminal, alpha helical domain of fungal Ure2p Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Ure2p subfamily; composed of the Saccharomyces cerevisiae Ure2p and related fungal 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. 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.

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gi 696410465 123 EQRDPALIEESKKQCDALFGILDAELAKT--PWLSGDAFGIADMAPAP---HIYNLFNVGIEW--TPRPHLERWYQQLTE 195
Cdd:cd10293   31 AEKVPSAIERYTNEIRRVLGVLETALAERyrVWLVGDKFTIADLAFVPwnnVVDMIFIDPELDikKEFPHVYKWLKRMLA 110

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gi 696410465 196 RPAFR 200
Cdd:cd10293  111 RPAVK 115

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 696410465  44 YLEMNPNGLVPCLRDDEtGLVLWESNAIVRYL 75
Cdd:cd03055   58 FLEKNPQGKVPALEIDE-GKVVYESLIICEYL 88