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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401864  91 LQRAVVDQRLHFESGVVFVNgLRGITKPLFATGQTtIPKERYDAVIEIYDFVETFLTGHDFIAGDQLTIADFSLITSITA 170
Cdd:cd03177    1 KKRAIVNQRLFFDSGTLYQR-LRDYYYPILFGGAE-PPEEKLDKLEEALEFLETFLEGSDYVAGDQLTIADLSLVATVST 78

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 665401864 171 LAVfVVIDTVKYANITAWIKRIEELPYYEEACGKGARDL 209
Cdd:cd03177   79 LEV-VGFDLSKYPNVAAWYERLKALPPGEEENGEGAKEL 116

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 665401864    6 LYGTEASPPVRAAKLTLAALGIPYEYVKINtlaKETLSPEFLRKNPQHTVPTLEDDGHFIWDSHAISAYLVSKYGQS 82
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIP---PGDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYPGP 74

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401864  91 LQRAVVDQRLHFESGVVFVNgLRGITKPLFATGQTtIPKERYDAVIEIYDFVETFLTGHDFIAGDQLTIADFSLITSITA 170
Cdd:cd03177    1 KKRAIVNQRLFFDSGTLYQR-LRDYYYPILFGGAE-PPEEKLDKLEEALEFLETFLEGSDYVAGDQLTIADLSLVATVST 78

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 665401864 171 LAVfVVIDTVKYANITAWIKRIEELPYYEEACGKGARDL 209
Cdd:cd03177   79 LEV-VGFDLSKYPNVAAWYERLKALPPGEEENGEGAKEL 116

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 665401864   4 LILYGTEASPPVRAAKLTLAALGIPYEYVKINTLAKETLspEFLRKNPQHTVPTLEDDGHFIWDSHAISAYL 75
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQE--EFLALNPLGKVPVLEDGGLVLTESLAILEYL 70

maleylacetoacetate isomerase; Maleylacetoacetate isomerase is an enzyme of tyrosine and phenylalanine catabolism. It requires glutathione and belongs by homology to the zeta family of glutathione S-transferases. The enzyme (EC 5.2.1.2) is described as active also on maleylpyruvate, and the example from a Ralstonia sp. catabolic plasmid is described as a maleylpyruvate isomerase involved in gentisate catabolism. [Energy metabolism, Amino acids and amines]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401864    5 ILYG---TEASPPVRAAkltLAALGIPYEYVKINTLAK-ETLSPEFLRKNPQHTVPTLEDDGHFIWDSHAISAYLVSKYG 80
Cdd:TIGR01262   1 KLYSywrSSCSYRVRIA---LALKGIDYEYVPVNLLRDgEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYP 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401864   81 QSdTLYPKDLLQRAVVDQ-RLHFESGVVFVNGLRgITKPLFATGQTTiPKERY----DAVIEIYDFVETFLTGH--DFIA 153
Cdd:TIGR01262  78 DP-PLLPADPIKRARVRAlALLIACDIHPLNNLR-VLQYLREKLGVE-EEARNrwyqHWISKGFAALEALLQPHagRFCV 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 665401864  154 GDQLTIADFSLITSITALAVFVViDTVKYANITAWIKRIEELPYYEEA 201
Cdd:TIGR01262 155 GDTPTLADLCLVPQVYNAERFGV-DLTPYPTLRRIAAALAALPAFQRA 201

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 665401864   4 LILYG---TEASPPVRAAkltLAALGIPYEYVKINTLAKETLSPEFLRKNPQHTVPTLEDDGHFIWDSHAISAYL 75
Cdd:cd03042    1 MILYSyfrSSASYRVRIA---LNLKGLDYEYVPVNLLKGEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYL 72

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665401864   4 LILYGTEASPPVRAAKLTLAALGIPYEYVKINTLAKETLSPEFLRKNPQHTVPTLEDDGHFIWDSHAISAYLVSKY 79
Cdd:cd03050    1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

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 665401864   4 LILYGTEASPPVRAAkLTLAALGIPYEYVKINTLAKETLSPEFLRKNPQHTVPTLED---DGHFIWDSHAISAYLVSKYG 80
Cdd:cd03048    2 ITLYTHGTPNGFKVS-IMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDhngTPLTVFESGAILLYLAEKYD 80

                 .
gi 665401864  81 Q 81
Cdd:cd03048   81 K 81

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401864   6 LYG-TEASPPVRAAkLTLAALGIPYEYVKINTLAKETLSPEFLRKNPQHTVPTLEDDGHFIWDSHAISAYLVSKYG-QSD 83
Cdd:PLN02473   5 VYGqIKAANPQRVL-LCFLEKGIEFEVIHVDLDKLEQKKPEHLLRQPFGQVPAIEDGDLKLFESRAIARYYATKYAdQGT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401864  84 TLYPKDLLQRAVVDQRLHFESGVVFVNGL----RGITKPLFATGQTTIPKE----RYDAVIEIYdfvETFLTGHDFIAGD 155
Cdd:PLN02473  84 DLLGKTLEHRAIVDQWVEVENNYFYAVALplviNLVFKPRLGEPCDVALVEelkvKFDKVLDVY---ENRLATNRYLGGD 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 665401864 156 QLTIADFS------LITSITALAVFVvidtVKYANITAWIKRIEELPYYEE 200
Cdd:PLN02473 161 EFTLADLThmpgmrYIMNETSLSGLV----TSRENLNRWWNEISARPAWKK 207

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 665401864   4 LILYGTEASPPVRAAKLTLAALGIPYEYVKINTLAKETLSPEFLRKNPQHTVPTLEDDGHFIWDSHAISAYL 75
Cdd:cd03047    1 LTIWGRRSSINVQKVLWLLDELGLPYERIDAGGQFGGLDTPEFLAMNPNGRVPVLEDGDFVLWESNAILRYL 72

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401864   4 LILYGTEASPPVRAAkLTLAALGIPYEYVKINTLAKETLSPEFLRKNPQHTVPTLEDDGHFIWDSHAISAYLVSKY-GQS 82
Cdd:PLN02395   3 LKVYGPAFASPKRAL-VTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYrSQG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401864  83 DTLYPKDLLQRAVVDQRLHFESGVVFVNGLRGITKPLFA-----TGQTTIPKERYDAVIEIYDFVETFLTGHDFIAGDQL 157
Cdd:PLN02395  82 PDLLGKTIEERGQVEQWLDVEATSYHPPLLNLTLHILFAskmgfPADEKVIKESEEKLAKVLDVYEARLSKSKYLAGDFV 161

                 ....*.
gi 665401864 158 TIADFS 163
Cdd:PLN02395 162 SLADLA 167

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665401864   11 ASPPVRAAKLTLAALGIPYEYVKINTLAKETlSPEFLRKNPQHTVPTLED-DGHFIWDSHAISAYL 75
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLPYEIELVDLDPKDK-PPELLALNPLGTVPVLVLpDGTVLTDSLVILEYL 65

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 665401864 140 DFVETFLTGHDFIAGDQLTIADFSlITSITALAVFVVIDTVKYANITAWIKRIEELPYY 198
Cdd:cd03206   43 RLLDQHLAGRDWLAGDRPTIADVA-CYPYIALAPEGGVSLEPYPAIRAWLARVEALPGF 100

GST_N family, unknown subfamily 3; 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 665401864   6 LYGTEASPPVRAAKLTLA--ALGIPYEYVKINTLAKEtlsPEFLRKNPQHTVPTLE-DDGHFIWDSHAISAYL 75
Cdd:cd03049    3 LLYSPTSPYVRKVRVAAHetGLGDDVELVLVNPWSDD---ESLLAVNPLGKIPALVlDDGEALFDSRVICEYL 72

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401864   1 MSK--LILYGTE--ASPPVRAAKLTLAALGIPYEYVKINTLAKETLSPEFLRKNPQHTVPTLEDDGHFIWDSHAISAYLV 76
Cdd:PRK15113   1 MSKpaITLYSDAhfFSPYVMSAFVALQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLE 80

                         90       100
                 ....*....|....*....|....
gi 665401864  77 SKYGQSDT--LYPKDLLQRAVVDQ 98
Cdd:PRK15113  81 ERFAPPAWerIYPADLQARARARQ 104

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665401864   3 KLILYGTEASPPVRAAKLTLAALGIPYEYVKINTlaKETLSPEFLRKNPQHTVPTLEDDGHFI--WDSHAISAYL 75
Cdd:COG0695    1 KVTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDE--DPEAREELRERSGRRTVPVIFIGGEHLggFDEGELDALL 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665401864 129 KERYDAVIEIYDFVETFLTGHDFIAGDQLTIADFSLITSITALAVFVVIDTV--KYANITAWIKRI 192
Cdd:cd00299   35 EAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEALGPYYDLldEYPRLKAWYDRL 100

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 665401864  20 LTLAALGIPYEyVKINTLAKETLSPEFLRKNPQHTVPTLEDDGHFIWDSHAISAYL 75
Cdd:cd03043   18 LLLKAAGIPFE-EILVPLYTPDTRARILEFSPTGKVPVLVDGGIVVWDSLAICEYL 72

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 665401864   4 LILYGTEASPPVRAAKLTLAALGIPYEYVKINTLAKetlSPEFLRKNPQH-TVPTLEDDGHFIWDSHAISAYL 75
Cdd:cd03058    1 VKLLGAWASPFVLRVRIALALKGVPYEYVEEDLGNK---SELLLASNPVHkKIPVLLHNGKPICESLIIVEYI 70

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 665401864   6 LYGTEASPPVRAAKLTLAALGIPYEYVKiNTLAKETLSPEFLRKNPQHTVPTLE-DDGHFIWDSHAISAYLVSK 78
Cdd:cd03044    3 LYTYPGNPRSLKILAAAKYNGLDVEIVD-FQPGKENKTPEFLKKFPLGKVPAFEgADGFCLFESNAIAYYVANL 75

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 665401864 139 YDFVETFLTGHDFIAGDQLTIADFSLITsITALAVFVVIDTVKYANITAWIKRIEELP 196
Cdd:cd03188   51 LAYLDAQLAGGPYLLGDQFSVADAYLFV-VLRWARAVGLDLSDWPHLAAYLARVAARP 107

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401864 114 GITKPLFATGQttipkERYD-AVIEIY---DFVETFLTGHDFIAGDQLTIADFSLITSITAL-AVFVVI------DTVKY 182
Cdd:cd03190   22 GVYKAGFATTQ-----EAYDkAVKELFealDKLEKRLSKQPYLLGDRLTEADIRLFTTLIRFdPVYHQHfkcnlkTIRDY 96

                         90
                 ....*....|....
gi 665401864 183 ANITAWIKRIEELP 196
Cdd:cd03190   97 PNLWRYLRRLYQNP 110

C-terminal, alpha helical domain of Class Mu Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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 665401864 143 ETFLTGHDFIAGDQLTIADFSLITSITALAVFV--VIDtvKYANITAWIKRIEELP 196
Cdd:cd03209   48 SEFLGDRPWFAGDKITYVDFLLYEALDQHRIFEpdCLD--AFPNLKDFLERFEALP 101

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.

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gi 665401864   4 LILYGTEASPPVRAAKLTLAALGIPYEYVKIntlAKETLS-PEFLRKNPQHTVPTLED--DGHFIWDSHAISAYLVSKY 79
Cdd:cd03041    2 LELYEFEGSPFCRLVREVLTELELDVILYPC---PKGSPKrDKFLEKGGKVQVPYLVDpnTGVQMFESADIVKYLFKTY 77

Glutaredoxin-related protein [Posttranslational modification, protein turnover, chaperones];

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gi 665401864   3 KLILYGTEASPPVRAAKLTLAALGIPYEYVKI 34
Cdd:COG4545    2 KLILYGSELCPDCAPAKEELKELGIDYEFVDI 33

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 665401864 129 KERY-DAVIEIYDFVETFLTGH--DFIAGDQLTIADFSLIT---SITALAVFVVIDTVK-YANITAWIKRIEELPYYEEA 201
Cdd:cd10293   38 IERYtNEIRRVLGVLETALAERyrVWLVGDKFTIADLAFVPwnnVVDMIFIDPELDIKKeFPHVYKWLKRMLARPAVKKA 117