C-terminal, alpha helical domain of Class Theta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 the 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 the aryl or alkyl sulfate esters.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124  91 KRAQVDEFLSWQHTNIRSHGSKVFWFKGVLPAVTGAPVPKEKMDSALEDLNMSLKIFEDKFLQSRPFIIGDKISLADIVA 170
Cdd:cd03183     1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLPLFGGTPVSPEKVKKAEENLEESLDLLENKFLKDKPFLAGDEISIADLSA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1032199124 171 IVEMMQPVATGVDVFEGRPALSAWRDRVKKEvGVELFDEAHKVIMNV 217
Cdd:cd03183    81 ICEIMQPEAAGYDVFEGRPKLAAWRKRVKEA-GNPLFDEAHKVIYKL 126

C-terminal, alpha helical domain of Class Theta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 the 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 the aryl or alkyl sulfate esters.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124  91 KRAQVDEFLSWQHTNIRSHGSKVFWFKGVLPAVTGAPVPKEKMDSALEDLNMSLKIFEDKFLQSRPFIIGDKISLADIVA 170
Cdd:cd03183     1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLPLFGGTPVSPEKVKKAEENLEESLDLLENKFLKDKPFLAGDEISIADLSA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1032199124 171 IVEMMQPVATGVDVFEGRPALSAWRDRVKKEvGVELFDEAHKVIMNV 217
Cdd:cd03183    81 ICEIMQPEAAGYDVFEGRPKLAAWRKRVKEA-GNPLFDEAHKVIYKL 126

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124   3 LELYLDLHSQPCRSVFIFAKINKIPFEYKAVDLSAGEQYGDEFGKVSIIRKVPALKDGDFLLTESIAILLYLAGKHSTPd 82
Cdd:COG0625     2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEP- 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124  83 HWYPADLQKRAQVDEFLSWQHTNIRSHGSKVFWfkgvlpAVTGAPVPkEKMDSALEDLNMSLKIFEDKfLQSRPFIIGDK 162
Cdd:COG0625    81 PLLPADPAARARVRQWLAWADGDLHPALRNLLE------RLAPEKDP-AAIARARAELARLLAVLEAR-LAGGPYLAGDR 152

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1032199124 163 ISLADIVAIVEMMQPVATGVDVfEGRPALSAWRDRVK 199
Cdd:COG0625   153 FSIADIALAPVLRRLDRLGLDL-ADYPNLAAWLARLA 188

putative S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124  29 EYKA--VDLSAGEQYGDEFGKVSIIRKVPALKD--GD--FLLTESIAILLYLAGKHstpDHWYPADLQKRAQVdefLSWq 102
Cdd:PRK11752   74 EYDAwlIRIGEGDQFSSGFVEINPNSKIPALLDrsGNppIRVFESGAILLYLAEKF---GAFLPKDLAARTET---LNW- 146

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124 103 htnirshgskVFWFKGVLPAVTG--------APvpkEKMDSALEDLNMSLKI---FEDKFLQSRPFIIGDKISLADIvAI 171
Cdd:PRK11752  147 ----------LFWQQGSAPFLGGgfghfyayAP---EKIEYAINRFTMEAKRqldVLDKQLAEHEYIAGDEYTIADI-AI 212

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124 117 KGVLPAVTGAPVPKEKMDSALEDLNMSLKIFEDKfLQSRPFIIGDKISLADIVA--IVEMMQPVATGVdVFEGRPALSAW 194
Cdd:pfam00043   8 IALLPYVPPEEKKEPEVDEALEKVARVLSALEEV-LKGQTYLVGDKLTLADIALapALLWLYELDPAC-LREKFPNLKAW 85

                  ....
gi 1032199124 195 RDRV 198
Cdd:pfam00043  86 FERV 89

C-terminal, alpha helical domain of Class Theta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 the 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 the aryl or alkyl sulfate esters.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124  91 KRAQVDEFLSWQHTNIRSHGSKVFWFKGVLPAVTGAPVPKEKMDSALEDLNMSLKIFEDKFLQSRPFIIGDKISLADIVA 170
Cdd:cd03183     1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLPLFGGTPVSPEKVKKAEENLEESLDLLENKFLKDKPFLAGDEISIADLSA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1032199124 171 IVEMMQPVATGVDVFEGRPALSAWRDRVKKEvGVELFDEAHKVIMNV 217
Cdd:cd03183    81 ICEIMQPEAAGYDVFEGRPKLAAWRKRVKEA-GNPLFDEAHKVIYKL 126

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124   3 LELYLDLHSQPCRSVFIFAKINKIPFEYKAVDLSAGEQYGDEFGKVSIIRKVPALKDGDFLLTESIAILLYLAGKHSTPd 82
Cdd:COG0625     2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEP- 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124  83 HWYPADLQKRAQVDEFLSWQHTNIRSHGSKVFWfkgvlpAVTGAPVPkEKMDSALEDLNMSLKIFEDKfLQSRPFIIGDK 162
Cdd:COG0625    81 PLLPADPAARARVRQWLAWADGDLHPALRNLLE------RLAPEKDP-AAIARARAELARLLAVLEAR-LAGGPYLAGDR 152

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1032199124 163 ISLADIVAIVEMMQPVATGVDVfEGRPALSAWRDRVK 199
Cdd:COG0625   153 FSIADIALAPVLRRLDRLGLDL-ADYPNLAAWLARLA 188

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 1032199124   3 LELYLDLHSQPCRSVFIFAKINKIPFEYKAVDLSAGEQygDEFGKVSIIRKVPALKDGDFLLTESIAILLYLA 75
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQ--EEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1032199124  25 KIPFEYKAVDLSAGEQYGDEFGKVSIIRKVPALKDGDFLLTESIAILLYL 74
Cdd:cd03042    23 GLDYEYVPVNLLKGEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYL 72

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 1032199124   2 PLELYLdlHSQPC-RSVFIFAKINKIPFEYKAVDLSAGEQYGDEFGKVSIIRKVPALKD---GDFLLTESIAILLYLAGK 77
Cdd:cd03048     1 MITLYT--HGTPNgFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDhngTPLTVFESGAILLYLAEK 78

                  .
gi 1032199124  78 H 78
Cdd:cd03048    79 Y 79

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 1032199124   3 LELYLDLHSQPCRSVFIFAKINKIPFEYKAVDLSAGEQYGDEFGKVSIIRKVPALKDGDFLLTESIAILLYLA 75
Cdd:cd03056     1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYLA 73

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1032199124  26 IPFEYKAVDLSAGEQYGDEFGKVSIIRKVPALKDGDFL-LTESIAILLYLAGKH 78
Cdd:cd03057    23 LPFELVRVDLRTKTQKGADYLAINPKGQVPALVLDDGEvLTESAAILQYLADLH 76

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1032199124   2 PLELYLDLHSQPCRSVFIFAKINKIPFEYKAVDLSAGEQYGDEFGKVSIIRKVPALKDGDFLLTESIAILLYLAGK 77
Cdd:cd03053     1 VLKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

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 1032199124 125 GAPVPKEKMD---SALEDLNmslkifedKFLQSRPFIIGDKISLADI--VAIVEMMqpVATGVDvFEGRPALSAWRDRVK 199
Cdd:cd03177    32 GAEPPEEKLDkleEALEFLE--------TFLEGSDYVAGDQLTIADLslVATVSTL--EVVGFD-LSKYPNVAAWYERLK 100

                          90
                  ....*....|....
gi 1032199124 200 KEV-GVELFDEAHK 212
Cdd:cd03177   101 ALPpGEEENGEGAK 114

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124  90 QKRAQVDEFLSWQHTNIRSHGSKVFWfkGVLPavtgapVPKEKMDSA-----LEDLNMSLKIFEDKfLQSRPFIIGDKIS 164
Cdd:cd03180     1 AQRALADRWMDWQTSTLNPAFRYAFW--GLVR------TPPEQRDPAaiaasLAACNKLMAILDAQ-LARQAYLAGDRFT 71

                  ....*
gi 1032199124 165 LADIV 169
Cdd:cd03180    72 LADIA 76

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124 117 KGVLPAVTGAPVPKEKMDSALEDLNMSLKIFEDKfLQSRPFIIGDKISLADIVA--IVEMMQPVATGVdVFEGRPALSAW 194
Cdd:pfam00043   8 IALLPYVPPEEKKEPEVDEALEKVARVLSALEEV-LKGQTYLVGDKLTLADIALapALLWLYELDPAC-LREKFPNLKAW 85

                  ....
gi 1032199124 195 RDRV 198
Cdd:pfam00043  86 FERV 89

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1032199124   5 LYLDLHSQPCRSVFIFAKINKIPFEYKAVDLsagEQYGDEFGKVSIIRKVPALKDGDFLLTESIAILLYLAGKHSTP 81
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPP---GDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYPGP 74

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1032199124   3 LELYlDLHSQPC-RSVFIFA--KINKIPFeyKAVDLSAGEQYGDEFGKVSIIRKVPALK--DGDFlLTESIAILLYL 74
Cdd:cd03051     1 MKLY-DSPTAPNpRRVRIFLaeKGIDVPL--VTVDLAAGEQRSPEFLAKNPAGTVPVLEldDGTV-ITESVAICRYL 73

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1032199124  37 AGEQYG----DEFGKVSIIRKVPALKDGDFLLTESIAILLYLA 75
Cdd:cd03047    31 AGGQFGgldtPEFLAMNPNGRVPVLEDGDFVLWESNAILRYLA 73

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124  28 FEYKAVDLSAGE-QYGDEFGKVSIIRKVPALK-DGDFLLTESIAILLYLAgkHSTPDHWY--PADLQKRAQVDEFLSWQH 103
Cdd:PRK10542   25 FTLVSVDLAKKRlENGDDYLAINPKGQVPALLlDDGTLLTEGVAIMQYLA--DSVPDRQLlaPVGSLSRYHTIEWLNYIA 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124 104 TNIrsHgskvfwfKGVLPaVTGAPVPKEKMDSALEDLNMSLKiFEDKFLQSRPFIIGDKISLADIVAIVEMMQPVATGVD 183
Cdd:PRK10542  103 TEL--H-------KGFTP-LFRPDTPEEYKPTVRAQLEKKFQ-YVDEALADEQWICGQRFTIADAYLFTVLRWAYAVKLN 171

                         170
                  ....*....|....*..
gi 1032199124 184 VfEGRPALSAWRDRVKK 200
Cdd:PRK10542  172 L-EGLEHIAAYMQRVAE 187

C-terminal, alpha helical domain of Class Lambda Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Lambda subfamily; composed of plant-specific class Lambda GSTs. GSTs are cytosolic, usually 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 Lambda subfamily was recently discovered, together with dehydroascorbate reductases (DHARs), as two outlying groups of the GST superfamily in Arabidopsis thaliana, which contain conserved active site cysteines. Characterization of recombinant A. thaliana proteins show that Lambda class GSTs are monomeric, similar to DHARs. They do not exhibit GSH conjugating or DHAR activities, but are active as thiol transferases, similar to glutaredoxins. Members of this subfamily were originally identified as encoded proteins of the In2-1 gene, which can be induced by treatment with herbicide safeners.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124  88 DLQKRAQVDEFLSWQHTnirshgskvfWFKGVLPAVTGAPVPKEkMDSALEDLNMSLKIFEDKflqsrPFIIGdKISLAD 167
Cdd:cd03203     1 DPAKREFADELLAYADT----------FTKAVYSALIKGDMTAE-AAAAFDYLENALSKFDDG-----PFFLG-QFSLVD 63

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1032199124 168 I--VAIVEMMQPVATGV---DVFEGRPALSAWRDRVKK 200
Cdd:cd03203    64 IayAPFIERFQIVLSELrnyDITAGRPNLAKWIEEMNK 101

glutathione dehydrogenase (ascorbate)

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124  14 CRSVFIFAKINKIPFEYKAVDLSAGEQYgdeFGKVSIIRKVPALKDGDFLLTESIAILLYLAGKHSTPDHWYPADlqkRA 93
Cdd:PLN02817   76 CQRVLLTLEEKHLPYDMKLVDLTNKPEW---FLKISPEGKVPVVKLDEKWVADSDVITQALEEKYPDPPLATPPE---KA 149

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1032199124  94 QVdeflswqhtnirshGSKVFwfkgvlPAVTGAPVPKEKMDSALEDLNMSLKIFEDKFLQSRPFIIGDKISLADI 168
Cdd:PLN02817  150 SV--------------GSKIF------STFIGFLKSKDPGDGTEQALLDELTSFDDYIKENGPFINGEKISAADL 204

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1032199124  12 QPCRSVFIFAKInkiPFEYKAVDLSAGEQYGDE----FGKVsiirkvPALKDGDFLLTESIAILLYLA 75
Cdd:cd03039    13 EPIRLLLADAGV---EYEDVRITYEEWPELDLKptlpFGQL------PVLEIDGKKLTQSNAILRYLA 71

Glutathione S-transferase C-terminal-like, alpha helical domain of Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 3; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein (AIMP) 3 subfamily; AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex that functions as a molecular hub to coordinate protein synthesis. There are three AIMPs, named AIMP1-3, which play diverse regulatory roles. AIMP3, also called p18 or eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1), contains a C-terminal domain with similarity to the C-terminal alpha helical domain of GSTs. It specifically interacts with methionyl-tRNA synthetase (MetRS) and is translocated to the nucleus during DNA synthesis or in response to DNA damage and oncogenic stress. In the nucleus, it interacts with ATM and ATR, which are upstream kinase regulators of p53. It appears to work against DNA damage in cooperation with AIMP2, and similar to AIMP2, AIMP3 is also a haploinsufficient tumor suppressor. AIMP3 transgenic mice have shorter lifespans than wild-type mice and they show characteristics of progeria, suggesting that AIMP3 may also be involved in cellular and organismal aging.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1032199124 126 APVPKEKMDSALEDLNmslkifedKFLQSRPFIIGDKISLADIV 169
Cdd:cd10305    20 PASDKADAKSLLKELN--------SYLQDRTYLVGHKLTLADVV 55

C-terminal, alpha helical domain of Class Sigma-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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-like members include the class II insect GSTs, S-crystallins from cephalopods, nematode-specific GSTs, 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. Members also include 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1032199124 116 FKGVLPAVTGAPVPKEKMDSALEDLNMSLKIFEdKFLQS--RPFIIGDKISLADIVAI-----VEMMQPvatgVDVFEGR 188
Cdd:cd03192    20 FAPYFYEPDGEEKKEKKKEFLEEALPKFLGKFE-KILKKsgGGYFVGDKLTWADLALFdvldyLLYLLP----KDLLEKY 94

                          90
                  ....*....|
gi 1032199124 189 PALSAWRDRV 198
Cdd:cd03192    95 PKLKALRERV 104