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 195444956   3 DFYYLPGSAPCRSVIMTAKAVGVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVE 75
Cdd:cd03045    2 DLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

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 195444956   3 DFYYLPGSAPCRSVIMTAKAVGVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVE 75
Cdd:cd03045    2 DLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

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 195444956   21 KAVGVELNKKllnlqaGEHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVEKYgKTDSLYPKCPKKRAvINQRLYF 100
Cdd:TIGR01262  26 EYVPVNLLRD------GEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETY-PDPPLLPADPIKRA-RVRALAL 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956  101 DMGTLYQSFANY-YYPQVFAKAPADPEAFKK-----IEAAFDFLNTFLEGQ--EYAAGDSLTVADIALVATVSTFEVASF 172
Cdd:TIGR01262  98 LIACDIHPLNNLrVLQYLREKLGVEEEARNRwyqhwISKGFAALEALLQPHagRFCVGDTPTLADLCLVPQVYNAERFGV 177

                         170
                  ....*....|...
gi 195444956  173 DISKYPNVNKWYE 185
Cdd:TIGR01262 178 DLTPYPTLRRIAA 190

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956  15 SVIMTAKAVGVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVEKYGKTD--SLYPKCPKKRA 92
Cdd:PRK15113  21 SAFVALQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAPPAweRIYPADLQARA 100

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 195444956  113 YYPQVFAKAPADPEAFKKIEAAFDFLNTFLEGQEYAAGDSLTVADIALV--ATVSTFEVASFDISKYPNVNKWYEN 186
Cdd:pfam00043  13 YVPPEEKKEPEVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIALApaLLWLYELDPACLREKFPNLKAWFER 88

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 195444956   3 DFYYLPGSAPCRSVIMTAKAVGVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVE 75
Cdd:cd03045    2 DLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

GST_N family, Class Theta subfamily; composed of eukaryotic class Theta GSTs and bacterial dichloromethane (DCM) dehalogenase. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Mammalian class Theta GSTs show poor GSH conjugating activity towards the standard substrates, CDNB and ethacrynic acid, differentiating them from other mammalian GSTs. GSTT1-1 shows similar cataytic activity as bacterial DCM dehalogenase, catalyzing the GSH-dependent hydrolytic dehalogenation of dihalomethanes. This is an essential process in methylotrophic bacteria to enable them to use chloromethane and DCM as sole carbon and energy sources. The presence of polymorphisms in human GSTT1-1 and its relationship to the onset of diseases including cancer is subject of many studies. Human GSTT2-2 exhibits a highly specific sulfatase activity, catalyzing the cleavage of sulfate ions from aralkyl sufate esters, but not from aryl or alkyl sulfate esters.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 195444956   4 FYYLPGSAPCRSVIMTAKAVGVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVEKY 77
Cdd:cd03050    3 LYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

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 195444956   21 KAVGVELNKKllnlqaGEHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVEKYgKTDSLYPKCPKKRAvINQRLYF 100
Cdd:TIGR01262  26 EYVPVNLLRD------GEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETY-PDPPLLPADPIKRA-RVRALAL 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956  101 DMGTLYQSFANY-YYPQVFAKAPADPEAFKK-----IEAAFDFLNTFLEGQ--EYAAGDSLTVADIALVATVSTFEVASF 172
Cdd:TIGR01262  98 LIACDIHPLNNLrVLQYLREKLGVEEEARNRwyqhwISKGFAALEALLQPHagRFCVGDTPTLADLCLVPQVYNAERFGV 177

                         170
                  ....*....|...
gi 195444956  173 DISKYPNVNKWYE 185
Cdd:TIGR01262 178 DLTPYPTLRRIAA 190

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956   1 MADFYYLPgSAPCRSVIMTAKAVGVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLVDNG-------FALWESRAIQVYL 73
Cdd:PRK13972   1 MIDLYFAP-TPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSpadggepLSLFESGAILLYL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956  74 VEKYGktdSLYPKCPKKRAVINQRLYFDMGTLYQSFA-----NYYYPQVFakaPADPEAFK-KIEAAFDFLNTFLEGQEY 147
Cdd:PRK13972  80 AEKTG---LFLSHETRERAATLQWLFWQVGGLGPMLGqnhhfNHAAPQTI---PYAIERYQvETQRLYHVLNKRLENSPW 153

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 195444956 148 AAGDSLTVADIALVATVSTFEVASFDISKYPNVNKWYENAK 188
Cdd:PRK13972 154 LGGENYSIADIACWPWVNAWTRQRIDLAMYPAVKNWHERIR 194

putative S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956  24 GVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLVDNG----FALWESRAIQVYLVEKYGKtdsLYPKCPKKRAVINQRLY 99
Cdd:PRK11752  72 GAEYDAWLIRIGEGDQFSSGFVEINPNSKIPALLDRSgnppIRVFESGAILLYLAEKFGA---FLPKDLAARTETLNWLF 148

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956 100 FDMGT---LYQSFANYYypqvfAKAPadpeafKKIEAA-----------FDFLNTFLEGQEYAAGDSLTVADIAL----- 160
Cdd:PRK11752 149 WQQGSapfLGGGFGHFY-----AYAP------EKIEYAinrftmeakrqLDVLDKQLAEHEYIAGDEYTIADIAIwpwyg 217

                        170       180
                 ....*....|....*....|....*..
gi 195444956 161 -VATVSTFEVASF-DISKYPNVNKWYE 185
Cdd:PRK11752 218 nLVLGNLYDAAEFlDVGSYKHVQRWAK 244

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 195444956   4 FYYLPGSapcRS--VIMTAKAVGVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVEKYG 78
Cdd:cd03046    3 LYHLPRS---RSfrILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 76

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 195444956  94 INQRLYFDMGTLYQSFANYYYPQVFAKAP---ADPEAFKKIEAAFDFLNTFLEGQEYAAGDSLTVADIALVATVSTFEVA 170
Cdd:cd00299    1 VRALEDWADATLAPPLVRLLYLEKVPLPKdeaAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEAL 80

                         90
                 ....*....|....*....
gi 195444956 171 ---SFDISKYPNVNKWYEN 186
Cdd:cd00299   81 gpyYDLLDEYPRLKAWYDR 99

GST_N family, unknown subfamily 4; composed of uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 195444956  36 AGEHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYL 73
Cdd:cd03056   35 KGETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYL 72

C-terminal, alpha helical domain of Ure2p and related Glutathione S-transferase-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p, YfcG and YghU from Escherichia coli, and related GST-like 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. YfcG and YghU are two of the nine GST homologs in the genome of Escherichia coli. They display very low or no GSH transferase, but show very good disulfide bond oxidoreductase activity. YghU also shows modest organic hydroperoxide reductase 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 195444956  90 KRAVINQRLYFDMGTLYQSFANYYYPQVFAKAPaDPEAFKK----IEAAFDFLNTFLEGQEYAAGDSLTVADIALVATVS 165
Cdd:cd03178    1 ERAEVLQWLFFQMSGLGPMFGQAGHFLYFAPEK-IPYAIERytdeVKRLYGVLDKRLSDRPYLAGEEYSIADIALYPWTH 79

                         90       100
                 ....*....|....*....|.
gi 195444956 166 TFEVASF-DISKYPNVNKWYE 185
Cdd:cd03178   80 YADLGGFaDLSEYPNVKRWLE 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 195444956   4 FYYLPGSAPCRSVIMTAKAVGVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLV-DNGFALWESRAIQVYL 73
Cdd:cd03051    3 LYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLElDDGTVITESVAICRYL 73

GST_N family, Class Beta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit limited GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they also bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 195444956   4 FYYLPGSAPCRSVIMTAKAvGVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLV-DNGFALWESRAIQVYLVEKY 77
Cdd:cd03057    3 LYYSPGACSLAPHIALEEL-GLPFELVRVDLRTKTQKGADYLAINPKGQVPALVlDDGEVLTESAAILQYLADLH 76

Glutathione S-transferase C-terminal-like, alpha helical domain of the Gamma subunit of Elongation Factor 1B and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Gamma subunit of Elongation Factor 1B (EF1Bgamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds to membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression. Also included in this subfamily is the GST_C-like domain at the N-terminus of human valyl-tRNA synthetase (ValRS) and its homologs. Metazoan ValRS forms a stable complex with Elongation Factor-1H (EF-1H), and together, they catalyze consecutive steps in protein biosynthesis, tRNA aminoacylation and its transfer to EF.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956 108 SFANYYYPQVFaKAPADP----EAFKKIEAAFDFLNTFLEGQEYAAGDSLTVADIALVATVSTFEVASFD---ISKYPNV 180
Cdd:cd03181   19 AAATWVLPLLG-IAPYNKkavdKAKEDLKRALGVLEEHLLTRTYLVGERITLADIFVASALLRGFETVLDpefRKKYPNV 97

                 ....*
gi 195444956 181 NKWYE 185
Cdd:cd03181   98 TRWFN 102

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 195444956    5 YYLPGSAPCRSVIMTAKAVGVELNKKLLNLQageHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVEKYG 78
Cdd:pfam13417   2 YGFPGSPYARRVRIALNEKGLPYEFVPIPPG---DHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYP 72

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956  24 GVELNKKLLNLQAGEHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVEKYG-KTDSLYPKCPKKRAVINQrlYFDM 102
Cdd:PLN02473  25 GIEFEVIHVDLDKLEQKKPEHLLRQPFGQVPAIEDGDLKLFESRAIARYYATKYAdQGTDLLGKTLEHRAIVDQ--WVEV 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956 103 GTLYqsFANYYYPQVF-------AKAPAD---PEAFK-KIEAAFDFLNTFLEGQEYAAGDSLTVADIALVATVStFEVAS 171
Cdd:PLN02473 103 ENNY--FYAVALPLVInlvfkprLGEPCDvalVEELKvKFDKVLDVYENRLATNRYLGGDEFTLADLTHMPGMR-YIMNE 179

                        170       180
                 ....*....|....*....|....*...
gi 195444956 172 FDISKY----PNVNKWYENAKKvTPGWE 195
Cdd:PLN02473 180 TSLSGLvtsrENLNRWWNEISA-RPAWK 206

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 195444956 105 LYQSFANYYYPQVFAKApaDPEAFKKIEAA----FDFLNTFLE--GQEYAAGDSLTVADIALVATVSTFEVA--SFDISK 176
Cdd:cd03192   16 LRAEFAPYFYEPDGEEK--KEKKKEFLEEAlpkfLGKFEKILKksGGGYFVGDKLTWADLALFDVLDYLLYLlpKDLLEK 93

                 ....*....
gi 195444956 177 YPNVNKWYE 185
Cdd:cd03192   94 YPKLKALRE 102

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.

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gi 195444956   2 ADFYylpgSAPCRSViMTAKAVGVELnkKLLNLQageHLKPEFLKINPQHTIPTLVDNGFALWESRAIQVYLVEKY 77
Cdd:cd03059    8 DDVY----SHRVRIV-LAEKGVSVEI--IDVDPD---NPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDERF 73

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.

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gi 195444956 129 KKIEAAFDFLNTFLEGQEYAAGDSLTVADIALVATVSTFEVASFDI-SKYPNVNKWYE 185
Cdd:cd03182   51 KRVIDFLPVLDKRLAESPYVAGDRFSIADITAFVALDFAKNLKLPVpEELTALRRWYE 108

GST_N family, Gamma subunit of Elongation Factor 1B (EFB1gamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal TRX-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression.

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gi 195444956  20 AKAVGVELNkkLLNLQAGEHLK-PEFLKINPQHTIPTLV-DNGFALWESRAIQVYLVEK 76
Cdd:cd03044   19 AKYNGLDVE--IVDFQPGKENKtPEFLKKFPLGKVPAFEgADGFCLFESNAIAYYVANL 75

C-terminal, alpha helical domain of an unknown subfamily 7 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 7; composed of uncharacterized proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

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gi 195444956 120 KAPADPEAFKKI-EAAFDFLNTFLEGQEYAAGDSLTVADIALVATVSTFEVASFDISKYPNVNKWYENAKKVtPG 193
Cdd:cd03206   26 GAPLDPERARAIsHRLLRLLDQHLAGRDWLAGDRPTIADVACYPYIALAPEGGVSLEPYPAIRAWLARVEAL-PG 99

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.

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gi 195444956 121 APADPEAFKKIEAAFDFLNTFLEGQEYAAGDSLTVADIaLVATVSTFEVASFDISKYPNVNKWYE 185
Cdd:cd03207   31 EPAIAAAYGDLDERLAALEAALAGRPYLVGERFSAADL-LLASVLRWARAFGLLPEYPALRAYVA 94

C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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.

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gi 195444956 131 IEAAFDFLNTFLEGQE--YAAGDSLTVADIALVATVSTFEVASFDISKYPNVNKWYENAKK 189
Cdd:cd03191   49 IERGFQALEKLLASTAgkYCVGDEPTLADICLVPQVYNARRFGVDLSPYPTIVRINEACLE 109

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.

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gi 195444956 118 FAKAPAD-PEAFKKIEAAFDFLNTFLEGQEYAAGDSLTVADIALVATVSTFEVASFD--------ISKYPNVNKW 183
Cdd:cd03190   28 FATTQEAyDKAVKELFEALDKLEKRLSKQPYLLGDRLTEADIRLFTTLIRFDPVYHQhfkcnlktIRDYPNLWRY 102

Glutathione S-transferase C-terminal-like, alpha helical domain of bifunctional Glutamyl-Prolyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, bifunctional GluRS-Prolyl-tRNA synthetase (GluProRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of GluProRS from higher eukaryotes. Aminoacyl-tRNA synthetases (aaRSs) comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. The GST_C-like domain of GluProRS may be involved in protein-protein interactions, mediating the formation of the multi-aaRS complex in higher eukaryotes. The multi-aaRS complex acts as a molecular hub for protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

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gi 195444956 131 IEAAFDFLNTFLEGQEYAAGDSLTVADIALVATVSTFEVASFDISKYPNVNKWYE 185
Cdd:cd10309   22 FSSALSYLDKALSLRTYLVGNSLTLADFAVWAALRGNGEWLASKEKYVNVTRWFK 76

C-terminal, alpha helical domain of Escherichia coli Yghu Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YghU-like subfamily; composed of the Escherichia coli YghU 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. YghU is one of nine GST homologs in the genome of Escherichia coli. It is similar to Escherichia coli YfcG in that it has poor GSH transferase activity towards typical substrates. It shows modest reductase activity towards some organic hydroperoxides. Like YfcG, YghU also shows good disulfide bond oxidoreductase activity comparable to the activities of glutaredoxins and thioredoxins. YghU 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 YghU reveals two GSH molecules bound in its active site.

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gi 195444956 136 DFLNTFLEGQEYAAGDSLTVADIAL------VATVSTFEVASF-DISKYPNVNKWYEN 186
Cdd:cd10292   50 DVLDRQLATHKYLAGDEYTIADMAIwpwyggLALGSLYDAAEFlDVDEYKHVQRWAKD 107

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.

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gi 195444956 121 APADPEAfkKIEAAFDFLNTFLEGQEYAAGDSLTVADIALVATVSTFeVASFDI---SKYPNVNKWYEN 186
Cdd:cd10305   19 APASDKA--DAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLHPI-MKDLSPqekEQYLNVSRWFDH 84