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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662715271   95 DLQKRARARQIQAWLRSDLVPIRTERSTDVVFAGVKKPALSEEGLSSARKLIETASSLLAQGNPNLFGEWCIADTDLALM 174
Cdd:pfam14834   1 DLEKRARARQIQAWLRSDLMPIREERPTAVVFAGAKKADLSAAGKASAEKLFATAEHLLAHGGPNLFGEWCIADADLALM 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 662715271  175 LNRLILNGDDVPQLLVDYATFQWQRASVQRYLALSAK 211
Cdd:pfam14834  81 INRLVLHGDEVPEALADYASFQWQRASIQRFIALSAK 117

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662715271   6 ITLWSDanFFSPYVMSVYVALAEKGLTFSLKTVDLDSGEHLKPQWQGYALTRRVPVLEIDGFELSESSAIDEYLEDRFAP 85
Cdd:COG0625    2 MKLYGS--PPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662715271  86 PeweRIYPHDLQKRARARQIQAWLRSDLVP-IRTERStdvVFAGVKKPALSEEGLSSARKLIETASSLLAQGnPNLFGE- 163
Cdd:COG0625   80 P---PLLPADPAARARVRQWLAWADGDLHPaLRNLLE---RLAPEKDPAAIARARAELARLLAVLEARLAGG-PYLAGDr 152

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 662715271 164 WCIADTDLALMLNRLILNGDDVPQL--LVDYATFQWQRASVQRYLA 207
Cdd:COG0625  153 FSIADIALAPVLRRLDRLGLDLADYpnLAAWLARLAARPAFQRALA 198

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662715271   95 DLQKRARARQIQAWLRSDLVPIRTERSTDVVFAGVKKPALSEEGLSSARKLIETASSLLAQGNPNLFGEWCIADTDLALM 174
Cdd:pfam14834   1 DLEKRARARQIQAWLRSDLMPIREERPTAVVFAGAKKADLSAAGKASAEKLFATAEHLLAHGGPNLFGEWCIADADLALM 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 662715271  175 LNRLILNGDDVPQLLVDYATFQWQRASVQRYLALSAK 211
Cdd:pfam14834  81 INRLVLHGDEVPEALADYASFQWQRASIQRFIALSAK 117

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662715271   6 ITLWSDanFFSPYVMSVYVALAEKGLTFSLKTVDLDSGEHLKPQWQGYALTRRVPVLEIDGFELSESSAIDEYLEDRFAP 85
Cdd:COG0625    2 MKLYGS--PPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPE 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662715271  86 PeweRIYPHDLQKRARARQIQAWLRSDLVP-IRTERStdvVFAGVKKPALSEEGLSSARKLIETASSLLAQGnPNLFGE- 163
Cdd:COG0625   80 P---PLLPADPAARARVRQWLAWADGDLHPaLRNLLE---RLAPEKDPAAIARARAELARLLAVLEARLAGG-PYLAGDr 152

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 662715271 164 WCIADTDLALMLNRLILNGDDVPQL--LVDYATFQWQRASVQRYLA 207
Cdd:COG0625  153 FSIADIALAPVLRRLDRLGLDLADYpnLAAWLARLAARPAFQRALA 198

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 662715271   6 ITLWSDANffSPYVMSVYVALAEKGLTFSLKTVDLDSGEHLkpQWQGYALTRRVPVLEIDGFELSESSAIDEYLE 80
Cdd:cd00570    1 LKLYYFPG--SPRSLRVRLALEEKGLPYELVPVDLGEGEQE--EFLALNPLGKVPVLEDGGLVLTESLAILEYLA 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 662715271  22 VYVALAEKGLTFSLKTVDLDSGEHLKPQWQGYALTRRVPVLEIDGFELSESSAIDEYLE 80
Cdd:cd03042   15 VRIALNLKGLDYEYVPVNLLKGEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYLD 73

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 662715271   15 FSPYVMSVYVALAEKGLTFSLKTVDLDsGEHLKPQWQGYALTRRVPVLE-IDGFELSESSAIDEYLEDR 82
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLPYEIELVDLD-PKDKPPELLALNPLGTVPVLVlPDGTVLTDSLVILEYLEEL 68

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 662715271  16 SPYVMSVYVALAEKGLTFSLKTVDLDSGEHLKPQWQGYALTRRVPVLEIDGFELSESSAIDEYL 79
Cdd:cd03045    9 SPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYL 72

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 662715271  22 VYVALAEKGLTFSLKTVDLDSGEHLKPQwqgyALTR----RVPVLEIDGFELSESSAIDEYLEDRFA 84
Cdd:cd03046   14 ILWLLEELGLPYELVLYDRGPGEQAPPE----YLAInplgKVPVLVDGDLVLTESAAIILYLAEKYG 76

GST_N family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p and related GSTs. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The N-terminal TRX-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. Characterized GSTs in this subfamily include Aspergillus fumigatus GSTs 1 and 2, and Schizosaccharomyces pombe GST-I. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of GSH with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662715271   6 ITLWSDAnffSPYVMSVYVALAEKGLTFSLKTVDLDSGEHLKPQWQGYALTRRVPVL---EIDGFELSESSAIDEYLEDR 82
Cdd:cd03048    2 ITLYTHG---TPNGFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIvdhNGTPLTVFESGAILLYLAEK 78

                 .
gi 662715271  83 F 83
Cdd:cd03048   79 Y 79

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662715271   6 ITLWSDANffSPYVMSVYVALAEKGLTFSLKTVDLDS-GEHL---KPQWQgyaltrrVPVLEIDGFELSESSAIDEYLED 81
Cdd:cd03059    1 MTLYSGPD--DVYSHRVRIVLAEKGVSVEIIDVDPDNpPEDLaelNPYGT-------VPTLVDRDLVLYESRIIMEYLDE 71

                 ..
gi 662715271  82 RF 83
Cdd:cd03059   72 RF 73

stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662715271   3 QPVITLWSDANffSPYVMSVYVALAEKGLTFSLKTVDLDSGEH----LKPQwqgyaltRRVPVLEIDGFELSESSAIDEY 78
Cdd:PRK09481   8 RSVMTLFSGPT--DIYSHQVRIVLAEKGVSVEIEQVEKDNLPQdlidLNPY-------QSVPTLVDRELTLYESRIIMEY 78

                         90
                 ....*....|....*
gi 662715271  79 LEDRFAPPEWERIYP 93
Cdd:PRK09481  79 LDERFPHPPLMPVYP 93

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 662715271  15 FSPYVMSVYVALAEKGLTFSLKTVDLDSGEhLKPQWQGYALTRRVPVLEIDGFELSESSAIDEYL 79
Cdd:cd03043    9 YSSWSLRPWLLLKAAGIPFEEILVPLYTPD-TRARILEFSPTGKVPVLVDGGIVVWDSLAICEYL 72

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 662715271  17 PYVMSVYVALAEKGLTFSLKTVDLDSgehlKPQW------QGyaltrRVPVLEIDGFELSESSAIDEYLEDRFAPP 86
Cdd:PLN02817  74 PFCQRVLLTLEEKHLPYDMKLVDLTN----KPEWflkispEG-----KVPVVKLDEKWVADSDVITQALEEKYPDP 140

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 662715271 102 ARQIQAWLRSDLVPIRTERSTDVVFAGVKKPALSEEGLSSARKLIETASSLLAQGNPNLFGEWCIADTDLALMLNRLILN 181
Cdd:cd00299    1 VRALEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEAL 80

                 ....*
gi 662715271 182 GDDVP 186
Cdd:cd00299   81 GPYYD 85

C-terminal, alpha helical domain of an unknown subfamily 3 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 3; composed of uncharacterized proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 662715271  99 RARARQIQAWLRSDLVPIRTERSTDVvFAGVKKPALSEEGLSSARKLIETASSLLAQ---GNPNLFGEWCIADTDLALML 175
Cdd:cd03194    4 RALARSACAEMHSGFSALRSACPMNL-RARRPGVELSPAVQADIARIEAIWTEARARfgaGGPFLFGEFSIADAFYAPVV 82

                         90       100       110
                 ....*....|....*....|....*....|..
gi 662715271 176 NRLILNGDDVPQLLVDYATFQWQRASVQRYLA 207
Cdd:cd03194   83 TRFRTYGVPLSPAARAYVEALLALPAMQEWIE 114