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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1386635257  26 LILYHWTHSFSSQKVRLVIAEKALKCEEHDVSLPLSEHNEPWFMRLNSTGEVPVLIHGENIICEATQIIDYLE 98
Cdd:cd03052     1 LVLYHWTQSFSSQKVRLVIAEKGLRCEEYDVSLPLSEHNEPWFMRLNPTGEVPVLIHGDNIICDPTQIIDYLE 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1386635257  26 LILYHWTHSFSSQKVRLVIAEKALKCEEHDVSLPLSEHNEPWFMRLNSTGEVPVLIHGENIICEATQIIDYLE 98
Cdd:cd03052     1 LVLYHWTQSFSSQKVRLVIAEKGLRCEEYDVSLPLSEHNEPWFMRLNPTGEVPVLIHGDNIICDPTQIIDYLE 73

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1386635257  28 LYHWTHSFSSQKVRLVIAEKALKCEEHDVSLplsEHNEPWFMRLNSTGEVPVLIHGENIICEATQIIDYLEQTF 101
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPP---GDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELY 71

glutathione dehydrogenase (ascorbate)

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1386635257  37 SQKVRLVIAEKALKCEEHDVSLPlsehNEP-WFMRLNSTGEVPVLIHGENIICEATQIIDYLEQTFLDGQIGNTESElkk 115
Cdd:PLN02817   76 CQRVLLTLEEKHLPYDMKLVDLT----NKPeWFLKISPEGKVPVVKLDEKWVADSDVITQALEEKYPDPPLATPPEK--- 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1386635257 116 lAEENPDLQEAYIAkqkRLKSKllDHDnvkylkkilDELEKVLdqvETELQRRNEETPEEGqqPWLCGESFTLADVSLAV 195
Cdd:PLN02817  149 -ASVGSKIFSTFIG---FLKSK--DPG---------DGTEQAL---LDELTSFDDYIKENG--PFINGEKISAADLSLGP 208

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1386635257 196 TLHRLKFLGFARRNWG-NGKRPNLETYYERVLKRKTFNKVLGHVNNIlisavlptafrVAKKRaPKVLG 263
Cdd:PLN02817  209 KLYHLEIALGHYKNWSvPDSLPFVKSYMKNIFSMESFVKTRALPEDV-----------IAGWR-PKVMG 265

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1386635257 121 PDLQEAYIAKQKRLKSKLLDHDNVKYLKKILDELEKVLDQVETELQRRNEETPEEGQQPWLCGESFTLADVSLAVTLHRL 200
Cdd:cd03204     1 PDLAEAYTAKQKKLAIQLRDHEDSSYLKKILDELEVVLDQVEKELGERKRETDESGQQQWLCGESFTAADISLSVLLHRL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1386635257 201 KFLGFARRNWGNGKRPNLETYYERVLKRKTF 231
Cdd:cd03204    81 KFLGLSRRFWGNGKRPNIESYFERVRQRESF 111

C-terminal, alpha helical domain of Ganglioside-induced differentiation-associated protein 1-like 1; Glutathione S-transferase (GST) C-terminal domain family, Ganglioside-induced differentiation-associated protein 1-like 1 (GDAP1L1) subfamily; GDAP1L1 is a paralogue of GDAP1 with about 56% sequence identity and 70% similarity. It's function is unknown. Like GDAP1, it does not exhibit GST activity using standard substrates. GDAP1 was originally identified as a highly expressed gene at the differentiated stage of GD3 synthase-transfected cells. More recently, mutations in GDAP1 have been reported to cause both axonal and demyelinating autosomal-recessive Charcot-Marie-Tooth (CMT) type 4A neuropathy. CMT is characterized by slow and progressive weakness and atrophy of muscles. Sequence analysis of GDAP1 shows similarities and differences with GSTs; it appears to contain both N-terminal thioredoxin-fold and C-terminal alpha helical domains of GSTs, however, it also contains additional C-terminal transmembrane domains unlike GSTs. GDAP1 is mainly expressed in neuronal cells and is localized in the mitochondria through its transmembrane domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1386635257 121 PDLQEAYIAKQKRLKSKLLDHDNVKYLKKILDELEKVLDQVETELQRRNEETPEEGQQPWLCGESFTLADVSLAVTLHRL 200
Cdd:cd10302     1 PQLTEPYLSKQKKLMAKILEHDNVNYLKKILGELAMVLDQIEAELEKRKLEYEGQKCELWLCGCIFTLADVLLGATLHRL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1386635257 201 KFLGFARRNWGNGKRPNLETYYERVLKRKTF 231
Cdd:cd10302    81 KFLGLSKKYWEDGSRPNLQSFFERVQKRYAF 111

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 1386635257  26 LILYHWTHSFSSQKVRLVIAEKALKCEEHDVSLPLSEHnePWFMRLNSTGEVPVLIHGENIICEATQIIDYLE 98
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQ--EEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

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 1386635257 126 AYIAKQKRLKSKLLDHDNVKYLKKILDELEKVLDQVETELQrrneetpeegQQPWLCGESFTLADVSLAVTLHRLKFLGF 205
Cdd:cd00299    13 APPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLA----------GRPYLAGDQFSLADVALAPVLARLEALGP 82

                          90       100
                  ....*....|....*....|
gi 1386635257 206 ARRNWgnGKRPNLETYYERV 225
Cdd:cd00299    83 YYDLL--DEYPRLKAWYDRL 100

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 1386635257  26 LILYHWTHSFSSQKVRLVIAEKALKCEEHDVSLPLSEHNEPWFMRLNSTGEVPVLIHGE-NIICEATQIIDYLE 98
Cdd:cd03051     1 MKLYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLELDDgTVITESVAICRYLE 74

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 1386635257  26 LILYHWTHSFSSQKVRLVIAEKALKCEEHDVSLPLSEHNEPWFMRLNSTGEVPVLIHGENIICEATQIIDYLE 98
Cdd:cd03042     1 MILYSYFRSSASYRVRIALNLKGLDYEYVPVNLLKGEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYLD 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1386635257 147 LKKILDELEKVLDQVETELqrrneetpeeGQQPWLCGESFTLADVSLAVTLHRLKFLGFArRNWgNGKRPNLETYYER 224
Cdd:pfam13410   2 LERAREQLRAALDALEARL----------ADGPGLLGDRPTLADIALAPVLARLDAAYPG-LDL-REGYPRLRAWLER 67

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 1386635257 151 LDELEKVLDQVETELQRrneetpeegqQPWLCGESFTLADVSLAVTLHRLKFLGFARRNwgngkRPNLETYYERVLKRKT 230
Cdd:cd03180    45 LAACNKLMAILDAQLAR----------QAYLAGDRFTLADIALGCSVYRWLELPIERPA-----LPHLERWYARLSQRPA 109

                  .
gi 1386635257 231 F 231
Cdd:cd03180   110 F 110

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 1386635257 141 HDNVKylKKILDELEKVLDQVETELQRRneetpeegqqPWLCGESFTLADVSLAVTLHRLKFLGFARRNWgngkrPNLET 220
Cdd:cd03188    36 AEEVK--AAARERLERRLAYLDAQLAGG----------PYLLGDQFSVADAYLFVVLRWARAVGLDLSDW-----PHLAA 98

                          90
                  ....*....|....*
gi 1386635257 221 YYERVLKRKTFNKVL 235
Cdd:cd03188    99 YLARVAARPAVQAAL 113

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 1386635257  25 KLILYHWTHSFSSQKVRLVIAEKALKCEEHDVSLPLSEHNEPWFMRLNSTGEVPVLIHGENIICEATQIIDYL 97
Cdd:cd03053     1 VLKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYL 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1386635257  26 LILYHWTHSfSSQKVRLVIAEKALKCEEHDVSLPLSEHNEPWFMRLNSTGEVPVLIHGENIICEATQIIDYL 97
Cdd:cd03046     1 ITLYHLPRS-RSFRILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYL 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1386635257 152 DELEKVLDQVETELQRRneetpeegqqPWLCGESFTLADVSLAVTlhrlkfLGFARRNWGNGKRPNLETYYERVLKR 228
Cdd:cd03207    39 GDLDERLAALEAALAGR----------PYLVGERFSAADLLLASV------LRWARAFGLLPEYPALRAYVARCTAR 99

glutathione transferase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1386635257  43 VIAEKALKCEEHDVSLPLSEHNEPWFMRLNSTGEVPVLIHGENIICEATQIIDYLEQTFldgqiGNTESElkklAEENPD 122
Cdd:PRK15113   25 ALQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERF-----APPAWE----RIYPAD 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1386635257 123 LQEAYIAKQKR--LKSKLL------DHDNVKYLKKI--LDEL-----EKVLDQVETELqrrneetPEEgqQPWLCGEsFT 187
Cdd:PRK15113   96 LQARARARQIQawLRSDLMplreerPTDVVFAGAKKapLSEAgkaaaEKLFAVAERLL-------APG--QPNLFGE-WC 165

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1386635257 188 LADVSLAVTLHRLKFLG---------FARRNWgngKRPNLETY 221
Cdd:PRK15113  166 IADTDLALMLNRLVLHGdevperladYATFQW---QRASVQRW 205

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1386635257  68 FMRLNSTGEVPVLIHGEN-IICEATQIIDYLEQTFLDGQI---GNTESELKKLAEENpdlqeaYIAKQ-KRLKSKLLDHD 142
Cdd:PRK10542   43 YLAINPKGQVPALLLDDGtLLTEGVAIMQYLADSVPDRQLlapVGSLSRYHTIEWLN------YIATElHKGFTPLFRPD 116

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1386635257 143 NVKYLKKILDE-LEKVLDQVETELQrrneetpeegQQPWLCGESFTLADVSLavtlhrlkflgFARRNWGNG------KR 215
Cdd:PRK10542  117 TPEEYKPTVRAqLEKKFQYVDEALA----------DEQWICGQRFTIADAYL-----------FTVLRWAYAvklnleGL 175

                         170
                  ....*....|...
gi 1386635257 216 PNLETYYERVLKR 228
Cdd:PRK10542  176 EHIAAYMQRVAER 188

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 1386635257 145 KYLKKILDELEKVLDQVETELqrrneetpeeGQQPWLCGESFTLADVSLAVTLHRLKFLGFarrNWGNGKRPNLETYYER 224
Cdd:pfam00043  22 PEVDEALEKVARVLSALEEVL----------KGQTYLVGDKLTLADIALAPALLWLYELDP---ACLREKFPNLKAWFER 88

                  ....
gi 1386635257 225 VLKR 228
Cdd:pfam00043  89 VAAR 92

C-terminal, alpha helical domain of GTT1-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. GTT1, a homodimer, exhibits GST activity with standard substrates and associates with the endoplasmic reticulum. Its expression is induced after diauxic shift and remains high throughout the stationary phase. S. pombe GST-III is implicated in the detoxification of various metals.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1386635257 153 ELEKVLDQVETELQRRneetpeegqqPWLCGESFTLADVSLAVTLhrlkfLGFARRNWGNGKRPNLETYYERVLKR 228
Cdd:cd03189    62 ELKRHLDFLEDHLAKH----------PYFAGDELTAADIMMSFPL-----EAALARGPLLEQYPNIAAYLERIEAR 122

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1386635257 142 DNVKYLKKILDELEKVLdqvetelqrrneetpeeGQQPWLCGESFTLADVSLAVTLHR 199
Cdd:cd03190    37 KAVKELFEALDKLEKRL-----------------SKQPYLLGDRLTEADIRLFTTLIR 77

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 1386635257 147 LKKILDELEKVLDQVETE-LQRRneetpeegqqPWLCGESFTLADVSLAVTLHRLKFLGfaRRNWGNgkRPNLETYYERV 225
Cdd:cd03183    43 VKKAEENLEESLDLLENKfLKDK----------PFLAGDEISIADLSAICEIMQPEAAG--YDVFEG--RPKLAAWRKRV 108

                  ...
gi 1386635257 226 LKR 228
Cdd:cd03183   109 KEA 111

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1386635257  36 SSQKVRLVIAEKALKCEEHDVSLPLSEHNEPWFMRLNSTGEVPVLIHGENIICEATQIIDYLEQTF------LDGQI--- 106
Cdd:PLN02395   12 SPKRALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYrsqgpdLLGKTiee 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1386635257 107 -GNTESELKKLAEE-NPDLQEAYIakQKRLKSKLLDHDNVKYLKKILDELEKVLDQVETELQRRNeetpeegqqpWLCGE 184
Cdd:PLN02395   92 rGQVEQWLDVEATSyHPPLLNLTL--HILFASKMGFPADEKVIKESEEKLAKVLDVYEARLSKSK----------YLAGD 159

                  ....*...
gi 1386635257 185 SFTLADVS 192
Cdd:PLN02395  160 FVSLADLA 167

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 1386635257 143 NVKYLKKILDELEKVLDQVETELqrrneetpeeGQQPWLCGESFTLADVSLAVTLHRLKFLGFARRnwgNGKRPNLETYY 222
Cdd:cd03187    39 DEAVVEENEAKLKKVLDVYEARL----------SKSKYLAGDSFTLADLSHLPNLHYLMATPSKKL---FDSRPHVKAWW 105

                          90
                  ....*....|...
gi 1386635257 223 ERVLKRKTFNKVL 235
Cdd:cd03187   106 EDISARPAWKKVL 118

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 1386635257  28 LYHWTHSFSSQKVRLVIAEKALKCE-EHDVSLPLSEHNEPwfMRLNSTGEVPVL-------IHGENIICE 89
Cdd:cd03049     3 LLYSPTSPYVRKVRVAAHETGLGDDvELVLVNPWSDDESL--LAVNPLGKIPALvlddgeaLFDSRVICE 70