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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017  96 EYYKLIQYLFFQASGQGVIWGQAGWFNFFHHEPVVSAVTRYRNEIKRVLGVLEDILKD--RDYLVANKYTIADLSFIPWN 173
Cdd:cd10293   1 EYYQAKQWLFFQASGQGPYWGQAGWFNVFHAEKVPSAIERYTNEIRRVLGVLETALAEryRVWLVGDKFTIADLAFVPWN 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 19076017 174 YNLGGLFGEgkfsfkeevPQLDFEKEFPKAYAWNQRLLARPAVKAT 219
Cdd:cd10293  81 NVVDMIFID---------PELDIKKEFPHVYKWLKRMLARPAVKKA 117

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017  96 EYYKLIQYLFFQASGQGVIWGQAGWFNFFHHEPVVSAVTRYRNEIKRVLGVLEDILKD--RDYLVANKYTIADLSFIPWN 173
Cdd:cd10293   1 EYYQAKQWLFFQASGQGPYWGQAGWFNVFHAEKVPSAIERYTNEIRRVLGVLETALAEryRVWLVGDKFTIADLAFVPWN 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 19076017 174 YNLGGLFGEgkfsfkeevPQLDFEKEFPKAYAWNQRLLARPAVKAT 219
Cdd:cd10293  81 NVVDMIFID---------PELDIKKEFPHVYKWLKRMLARPAVKKA 117

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 19076017   4 FTLYSHaGGPNPWKVVLALKELNLSYEQIFYDFQKGEQKCKEHLALNPNGRVPTLVDHKNNDYTIWESDAILIYLADKYD 83
Cdd:cd03048   2 ITLYTH-GTPNGFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDHNGTPLTVFESGAILLYLAEKYD 80

                .
gi 19076017  84 T 84
Cdd:cd03048  81 K 81

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 19076017     4 FTLYSHAGGPNPWKVVLALKELNLSYEQIFYDFQKGEQKCKEHLALNPNGRVPTLVDhknNDYTIWESDAILIYLAD 80
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALED---GGKKLTESRAILEYIAR 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19076017   139 EIKRVLGVLEDILKDRDYLVANKYTIADLSFIP---WNYNLGGLFGEGKfsfkeevpqldfekeFPKAYAWNQRLLARP 214
Cdd:pfam00043  30 KVARVLSALEEVLKGQTYLVGDKLTLADIALAPallWLYELDPACLREK---------------FPNLKAWFERVAARP 93

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017  96 EYYKLIQYLFFQASGQGVIWGQAGWFNFFHHEPVVSAVTRYRNEIKRVLGVLEDILKD--RDYLVANKYTIADLSFIPWN 173
Cdd:cd10293   1 EYYQAKQWLFFQASGQGPYWGQAGWFNVFHAEKVPSAIERYTNEIRRVLGVLETALAEryRVWLVGDKFTIADLAFVPWN 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 19076017 174 YNLGGLFGEgkfsfkeevPQLDFEKEFPKAYAWNQRLLARPAVKAT 219
Cdd:cd10293  81 NVVDMIFID---------PELDIKKEFPHVYKWLKRMLARPAVKKA 117

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 19076017   4 FTLYSHaGGPNPWKVVLALKELNLSYEQIFYDFQKGEQKCKEHLALNPNGRVPTLVDHKNNDYTIWESDAILIYLADKYD 83
Cdd:cd03048   2 ITLYTH-GTPNGFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDHNGTPLTVFESGAILLYLAEKYD 80

                .
gi 19076017  84 T 84
Cdd:cd03048  81 K 81

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017  96 EYYKLIQYLFFQASGQGVIWGQAGWFNFFHHEPVVSAVTRYRNEIKRVLGVLEDILKDRDYLVANKYTIADLSFIPWNYN 175
Cdd:cd10291   1 ERYAVLQWLMWQMGGLGPMQGQAHHFKRYAPEKIPYAIKRYTNETKRLYGVLDRRLAKSKYLAGDEYSIADIAIWPWVAR 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 19076017 176 LGGlfgegkfsfkeevpQLDFEKEFPKAYAWNQRLLARPAVKA 218
Cdd:cd10291  81 HEW--------------QGIDLADFPNLKRWFERLAARPAVQK 109

putative S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017    4 FTLYShAGGPNPWKVVLALKEL-NLSYEQIFYD-----FQKGEQKCKEHLALNPNGRVPTLVDHKNNDYT-IWESDAILI 76
Cdd:PRK11752  45 LQLYS-LGTPNGQKVTIMLEELlALGVKGAEYDawlirIGEGDQFSSGFVEINPNSKIPALLDRSGNPPIrVFESGAILL 123

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017   77 YLADKYDTdrkiSLSFDDPEYYKLIQYLFFQASGQGVIWGqaGWFNFFHHEPVV--SAVTRYRNEIKRVLGVLEDILKDR 154
Cdd:PRK11752 124 YLAEKFGA----FLPKDLAARTETLNWLFWQQGSAPFLGG--GFGHFYAYAPEKieYAINRFTMEAKRQLDVLDKQLAEH 197

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19076017  155 DYLVANKYTIADLSFIPW--NYNLGGLFGEGKFsfkeevpqLDFEkEFPKAYAWNQRLLARPAVK 217
Cdd:PRK11752 198 EYIAGDEYTIADIAIWPWygNLVLGNLYDAAEF--------LDVG-SYKHVQRWAKEIAERPAVK 253

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 19076017   4 FTLYSHAGGPNPWKVVLALKELNLSYEQIFYDFQKGEQKCKEHLALNPNGRVPTLVDHknnDYTIWESDAILIYLADK 81
Cdd:cd03053   2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDG---DLKLFESRAITRYLAEK 76

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19076017  18 VVLALKELNLSYEQIFYDFQKGEQKCKEHLALNPNGRVPTLVDHknnDYTIWESDAILIYLADKYD 83
Cdd:cd03046  14 ILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDG---DLVLTESAAIILYLAEKYG 76

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19076017   5 TLYSHAGGPNPWKVVLALKELNLSYEQIFYDFQKGEQKCKEHLALNPNGRVPTLVDhknNDYTIWESDAILIYLAD 80
Cdd:cd03045   2 DLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVD---NGFVLWESHAILIYLVE 74

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017   15 PWKVVLALKELNLSYEQIFYDFQKGEQKCKEHLALNPNGRVPTLVDhknNDYTIWESDAILIYLADKYDTDRKISLSFDD 94
Cdd:PLN02395  13 PKRALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVD---GDYKIFESRAIMRYYAEKYRSQGPDLLGKTI 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017   95 PEYYKLIQYLFFQASGQ---------GVIWGQAGWFnffhhEPVVSAVTRYRNEIKRVLGVLEDILKDRDYLVANKYTIA 165
Cdd:PLN02395  90 EERGQVEQWLDVEATSYhppllnltlHILFASKMGF-----PADEKVIKESEEKLAKVLDVYEARLSKSKYLAGDFVSLA 164

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 19076017  166 DLSFIPWNYNLGGLFGegkfsfkeevpQLDFEKEFPKAYAWNQRLLARPAVKATFE 221
Cdd:PLN02395 165 DLAHLPFTEYLVGPIG-----------KAYLIKDRKHVSAWWDDISSRPAWKEVLA 209

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 19076017  21 ALKELNLSYEQIFYDFQKGEQKCKEHLALNPNGRVPTLVDhkNNDYTIWESDAILIYLADKY 82
Cdd:cd03057  17 ALEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVL--DDGEVLTESAAILQYLADLH 76

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19076017  18 VVLALKELNLSYEQIFYDFQKGEQKCKEHLALNPNGRVPTLVDhknNDYTIWESDAILIYLADKY 82
Cdd:cd03050  15 VYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVD---GDFTLAESVAILRYLARKF 76

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017    6 LYSHAGGPNPWKVVLALKELNLSYEQIFYDFQKGEQKCKEHLALNPNGRVPTLVDhknNDYTIWESDAILIYLADKYdTD 85
Cdd:PLN02473   5 VYGQIKAANPQRVLLCFLEKGIEFEVIHVDLDKLEQKKPEHLLRQPFGQVPAIED---GDLKLFESRAIARYYATKY-AD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017   86 RKISLSFDDPEYYKL------IQYLFFQASGQGVIWGQAgwFNFFHHEPV-VSAVTRYRNEIKRVLGVLEDILKDRDYLV 158
Cdd:PLN02473  81 QGTDLLGKTLEHRAIvdqwveVENNYFYAVALPLVINLV--FKPRLGEPCdVALVEELKVKFDKVLDVYENRLATNRYLG 158

                        170
                 ....*....|...
gi 19076017  159 ANKYTIADLSFIP 171
Cdd:PLN02473 159 GDEFTLADLTHMP 171

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 19076017     5 TLYSHAGGPNPWKVVLALKELNLSYEQIFYDFQK-GEQKCKEHLALNPNGRVPTLVDhknNDYTIWESDAILIYLADKYD 83
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRdGEQRSPEFLALNPQGLVPTLDI---DGEVLTQSLAIIEYLEETYP 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017    84 TDRKISLsfDDPEYYKLIQYLFFQASG-QGViwGQAGWFNFFHHEPVVSAVTR---YRNEIKRVLGVLEDILKDR--DYL 157
Cdd:TIGR01262  78 DPPLLPA--DPIKRARVRALALLIACDiHPL--NNLRVLQYLREKLGVEEEARnrwYQHWISKGFAALEALLQPHagRFC 153

                         170
                  ....*....|....*...
gi 19076017   158 VANKYTIADLSFIPWNYN 175
Cdd:TIGR01262 154 VGDTPTLADLCLVPQVYN 171

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19076017  15 PWkvvLALKELNLSYEQIFYDFQKGEQKcKEHLALNPNGRVPTLVDHknnDYTIWESDAILIYLA 79
Cdd:cd03043  16 PW---LLLKAAGIPFEEILVPLYTPDTR-ARILEFSPTGKVPVLVDG---GIVVWDSLAICEYLA 73

C-terminal, alpha helical domain of an unknown subfamily 8 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 8; composed of Agrobacterium tumefaciens GST and other 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. The three-dimensional structure of Agrobacterium tumefaciens GST has been determined but there is no information on its functional characterization.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017 101 IQYLFFQASG-QGVIWGQA-GWFNFFHHEPVVSAVTRYRneIKRVLGVLEDILKDRDYLVANKYTIADLsfipwnyNLGG 178
Cdd:cd03207   2 LRWLFFAAGTvEPPLLNKAlGRFFEPPWGEPAIAAAYGD--LDERLAALEAALAGRPYLVGERFSAADL-------LLAS 72

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 19076017 179 LFGEG-KFSFKEEVPQLDfekefpkayAWNQRLLARPA 215
Cdd:cd03207  73 VLRWArAFGLLPEYPALR---------AYVARCTARPA 101

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19076017   139 EIKRVLGVLEDILKDRDYLVANKYTIADLSFIP---WNYNLGGLFGEGKfsfkeevpqldfekeFPKAYAWNQRLLARP 214
Cdd:pfam00043  30 KVARVLSALEEVLKGQTYLVGDKLTLADIALAPallWLYELDPACLREK---------------FPNLKAWFERVAARP 93

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 19076017 140 IKRVLGVLEDILKDRDYLVANKYTIADLSFIPwnyNLGGLfgegkfsfkeEVPQLDFEKeFPKAYAWNQRLLARPAVKAT 219
Cdd:cd03177  43 LEEALEFLETFLEGSDYVAGDQLTIADLSLVA---TVSTL----------EVVGFDLSK-YPNVAAWYERLKALPPGEEE 108

                ....*.
gi 19076017 220 FEELAK 225
Cdd:cd03177 109 NGEGAK 114

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 19076017  95 PEYYKLIQYLFFQASGQ----GVIWGQAGWFNFFHHEPVVSAVtryRNEIKRVLGVLEDILKDRDYLVANKYTIADL--- 167
Cdd:cd03188   1 LERARLLEWLNFIASELhkafGPLFYPARWADDALAEEVKAAA---RERLERRLAYLDAQLAGGPYLLGDQFSVADAylf 77

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 19076017 168 SFIPWNYNLGglfgegkfsfkeevpqLDFEkEFPKAYAWNQRLLARPAVKA 218
Cdd:cd03188  78 VVLRWARAVG----------------LDLS-DWPHLAAYLARVAARPAVQA 111

C-terminal, alpha helical domain of Class Phi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Tau 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017 132 AVTRYRNEIKRVLGVLEDILKDRDYLVANKYTIADLSFIPwnyNLGGLFGEGKFSFKEEVPQLDfekefpkayAWNQRLL 211
Cdd:cd03187  42 VVEENEAKLKKVLDVYEARLSKSKYLAGDSFTLADLSHLP---NLHYLMATPSKKLFDSRPHVK---------AWWEDIS 109

                ....*...
gi 19076017 212 ARPAVKAT 219
Cdd:cd03187 110 ARPAWKKV 117

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017  13 PNPWKVVLALKELNLSYEQIFYDFQKGEQKCKEHLAlNPNGRVPTLVDhkNNDYTIWESDAILIYLADKY 82
Cdd:cd03038  17 PNVWKTRLALNHKGLEYKTVPVEFPDIPPILGELTS-GGFYTVPVIVD--GSGEVIGDSFAIAEYLEEAY 83

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 19076017 102 QYLFFQASGQGVIWGQAGWFNFFHHEPVVSAVTRYRNEIKRVLGVLEDILKDRDYLVANKYTIADLSFIPWNYNLGGLFg 181
Cdd:cd00299   3 ALEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEALG- 81

                        90       100
                ....*....|....*....|....*....
gi 19076017 182 egkfsfkeevPQLDFEKEFPKAYAWNQRL 210
Cdd:cd00299  82 ----------PYYDLLDEYPRLKAWYDRL 100

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
                ....*....|....*....|....*....|.
gi 19076017 137 RNEIKRVLGVLEDILKDRDYLVANKYTIADL 167
Cdd:cd10305  24 KADAKSLLKELNSYLQDRTYLVGHKLTLADV 54

Glutathione S-transferase, C-terminal domain; This domain is closely related to pfam00043.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19076017   132 AVTRYRNEIKRVLGVLEDILKDRDYLVANKYTIADLSFIPWNYNLGGLFgegkfsfkeevPQLDFEKEFPKAYAW 206
Cdd:pfam13410   1 ALERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAAY-----------PGLDLREGYPRLRAW 64

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017 121 FNFFHH-EP---------VVSAVTRYRNEIKRVLGVLEDILKDRDYLVANKYTIADLSFipwnynLGGL-FGEgkfSFKE 189
Cdd:cd03182  24 FQAFRHaTPglkpdrevqVPEWGERNKKRVIDFLPVLDKRLAESPYVAGDRFSIADITA------FVALdFAK---NLKL 94

                        90       100
                ....*....|....*....|....*..
gi 19076017 190 EVPqldfeKEFPKAYAWNQRLLARPAV 216
Cdd:cd03182  95 PVP-----EELTALRRWYERMAARPSA 116

Glutathione S-transferase, C-terminal domain; This domain is closely related to pfam00043.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19076017   136 YRNE-IKRVLGVLEDILKDR--DYLVANKYTIADLSFipwnYNLGGLFGEGKFsfkeevpqLDFEKEFPKAYAWNQRLLA 212
Cdd:pfam14497  26 FREErLPKFLGYFEKVLNKNggGYLVGDKLTYADLAL----FQVLDGLLYPKA--------PDALDKYPKLKALHERVAA 93

                  ....*.
gi 19076017   213 RPAVKA 218
Cdd:pfam14497  94 RPNIKA 99