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 1243038490   1 MKLYFAPRTRATRARWLLEELEVPYELVKLDVAKQETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLADRFP 76
Cdd:cd03046     1 ITLYHLPRSRSFRILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 76

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1243038490   1 MKLY-FAPRTRATRARWLLEELEVPYELVKLDVAKQETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLAD 73
Cdd:pfam02798   3 LTLYgIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1243038490   1 MKLYFAPRTRATRARWLLEELEVPYELVKLDVAKQETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLADRFP 76
Cdd:cd03046     1 ITLYHLPRSRSFRILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 76

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 1243038490   1 MKLYFAPRTRATRARWLLEELEVPYELVKLDVAKQETTTPAHLALHPLGEVPVLV-DGATVLFESLAICLHLADRFP 76
Cdd:cd03057     1 MKLYYSPGACSLAPHIALEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVlDDGEVLTESAAILQYLADLHP 77

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 1243038490   1 MKLYFAPRTRAT-RARWLLEELEVPYELVKLDVAKQETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLADR 74
Cdd:cd03053     2 LKLYGAAMSTCVrRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1243038490   1 MKLY-FAPRTRATRARWLLEELEVPYELVKLDVAKQETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLAD 73
Cdd:pfam02798   3 LTLYgIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490   1 MKLYFAPRTRATRARWLLEELEVPYELVKLDVAKQETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLADRFpeKKL 80
Cdd:PLN02395    3 LKVYGPAFASPKRALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKY--RSQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490  81 APP---PGSADRGAYLQWIVFAEVTLDP----LVVEHYWNTQQ---PEEKKADLSRQhaRLNDVLEVLDVRLDGREFIAG 150
Cdd:PLN02395   81 GPDllgKTIEERGQVEQWLDVEATSYHPpllnLTLHILFASKMgfpADEKVIKESEE--KLAKVLDVYEARLSKSKYLAG 158

                  ....*...
gi 1243038490 151 DSFTAADV 158
Cdd:PLN02395  159 DFVSLADL 166

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1243038490  17 LLEELEVPYELVKLDVAKQETTTPAHLALHPLGEVPVLVD---GATVLFESLAICLHLADRFP 76
Cdd:cd03048    18 MLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDhngTPLTVFESGAILLYLAEKYD 80

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 1243038490   2 KLYFAPRTRATRARW-LLEELEVPYELVKLDVAKQETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLADRF 75
Cdd:cd03050     2 KLYYDLMSQPSRAVYiFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490   1 MKLYfAPRTRATRARWLLEELE--VPYELVKLDVAKQETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLADRFPEK 78
Cdd:PLN02473    3 VKVY-GQIKAANPQRVLLCFLEkgIEFEVIHVDLDKLEQKKPEHLLRQPFGQVPAIEDGDLKLFESRAIARYYATKYADQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490  79 KLAPPPGSADRGAYL-QWI----VFAEVTLDPLVVEHYWNTQQPEEKKADLSRQ-HARLNDVLEVLDVRLDGREFIAGDS 152
Cdd:PLN02473   82 GTDLLGKTLEHRAIVdQWVevenNYFYAVALPLVINLVFKPRLGEPCDVALVEElKVKFDKVLDVYENRLATNRYLGGDE 161

                  ....*.
gi 1243038490 153 FTAADV 158
Cdd:PLN02473  162 FTLADL 167

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1243038490  16 WLLEELEVPYELVklDVAKQ--ETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLA 72
Cdd:cd03047    17 WLLDELGLPYERI--DAGGQfgGLDTPEFLAMNPNGRVPVLEDGDFVLWESNAILRYLA 73

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490  82 PPPGSADRGAYLQWIVFAEVTLDP-----LVVEHYWNTQQPEE--------KKADLSRQHARLNDVLEVLDVRLDGREFI 148
Cdd:cd03189     1 PPPDTAEYADYLYWLHFAEGSLMPplllkLVFGKIGEAPPPFFrpisrkiaDKPLQAFINPELKRHLDFLEDHLAKHPYF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1243038490 149 AGDSFTAADVVLASILHLAHT-LKLLDGYPKLFEYTLRQAKRP 190
Cdd:cd03189    81 AGDELTAADIMMSFPLEAALArGPLLEQYPNIAAYLERIEARP 123

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 1243038490  16 WL-LEELEVPYE--LVKLDvakQETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLA 72
Cdd:cd03043    17 WLlLKAAGIPFEeiLVPLY---TPDTRARILEFSPTGKVPVLVDGGIVVWDSLAICEYLA 73

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 1243038490  94 QWIVFAEVTLDPLVVEHYWNTQQPEEKKADLSRQ-HARLNDVLEVLDVRLDGREFIAGDSFTAADVVLASILH----LAH 168
Cdd:cd00299     3 ALEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAaREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLArleaLGP 82

                          90
                  ....*....|....
gi 1243038490 169 TLKLLDGYPKLFEY 182
Cdd:cd00299    83 YYDLLDEYPRLKAW 96

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1243038490   2 KLYFAPR-TRATRARWLLEELEVPYELVKLDVAKqETTTPAHLALHPLGEVPVLV--DGaTVLFESLAICLHLA 72
Cdd:cd03044     2 TLYTYPGnPRSLKILAAAKYNGLDVEIVDFQPGK-ENKTPEFLKKFPLGKVPAFEgaDG-FCLFESNAIAYYVA 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1243038490   1 MKL-YFAPRTRATRARWLLEELEVPYElvklDVAKQETTTPAHLALH--PLGEVPVLVDGATVLFESLAICLHLAD 73
Cdd:cd03039     1 YKLtYFNIRGRGEPIRLLLADAGVEYE----DVRITYEEWPELDLKPtlPFGQLPVLEIDGKKLTQSNAILRYLAR 72

putative S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490  17 LLEEL------EVPYELVKLDVAKQETTTPAHLALHPLGEVPVLVDGATV----LFESLAICLHLADRFpeKKLAPPPGS 86
Cdd:PRK11752   61 MLEELlalgvkGAEYDAWLIRIGEGDQFSSGFVEINPNSKIPALLDRSGNppirVFESGAILLYLAEKF--GAFLPKDLA 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490  87 AdRGAYLQWiVFAEVTLDPLV---VEHYWNtQQPE-----------EKKadlsRQharlndvLEVLDVRLDGREFIAGDS 152
Cdd:PRK11752  139 A-RTETLNW-LFWQQGSAPFLgggFGHFYA-YAPEkieyainrftmEAK----RQ-------LDVLDKQLAEHEYIAGDE 204

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1243038490 153 FTAAD---------VVLASILHLAHTLKlLDGYPKLFEYTLRQAKRPATRRAV 196
Cdd:PRK11752  205 YTIADiaiwpwygnLVLGNLYDAAEFLD-VGSYKHVQRWAKEIAERPAVKRGR 256

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1243038490 124 LSRQHARLNDVLEVLDVRLDGREFIAGDSFTAADVVLASILHLAHT----LKLLDGYPKLFEY 182
Cdd:pfam13410   2 LERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAaypgLDLREGYPRLRAW 64

glutathione transferase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490  18 LEELEVPYELVKLDVAKQETTTPAHLALHPLGEVPVLVDGATVLFESLAICLHLADRFPEKKLAP--PPGSADRGAYLQW 95
Cdd:PRK15113   26 LQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAPPAWERiyPADLQARARARQI 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490  96 IVFAEVTLDPLVVEHYWNTQQPEEKKADLSRQ-HARLNDVLEVLDVRL-DGREFIAGDsFTAADVVLASILH-LAHTlkl 172
Cdd:PRK15113  106 QAWLRSDLMPLREERPTDVVFAGAKKAPLSEAgKAAAEKLFAVAERLLaPGQPNLFGE-WCIADTDLALMLNrLVLH--- 181

                         170       180
                  ....*....|....*....|...
gi 1243038490 173 LDGYP-KLFEYTLRQAKRPATRR 194
Cdd:PRK15113  182 GDEVPeRLADYATFQWQRASVQR 204

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 1243038490 115 QQPEEKKADLSRqhARLNDVLEVLDVRLDGREFIAGDSFTAADVV-LASILHLAHTL--KLLDGYPKLFEYTLRQAKRPA 191
Cdd:cd03187    36 LKTDEAVVEENE--AKLKKVLDVYEARLSKSKYLAGDSFTLADLShLPNLHYLMATPskKLFDSRPHVKAWWEDISARPA 113

                  ....*
gi 1243038490 192 TRRAV 196
Cdd:cd03187   114 WKKVL 118

glutathione dehydrogenase (ascorbate)

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490  18 LEELEVPYELVKLDVAKQETTtpaHLALHPLGEVPVLVDGATVLFESLAICLHLADRFPEKKLAPPPGSADRGA--YLQW 95
Cdd:PLN02817   83 LEEKHLPYDMKLVDLTNKPEW---FLKISPEGKVPVVKLDEKWVADSDVITQALEEKYPDPPLATPPEKASVGSkiFSTF 159

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490  96 IVFAEvTLDPlvvehywntqqpeekkADLSRQhARLNDVLEVLDVRLDGREFIAGDSFTAADVVLASILH 165
Cdd:PLN02817  160 IGFLK-SKDP----------------GDGTEQ-ALLDELTSFDDYIKENGPFINGEKISAADLSLGPKLY 211

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490 111 YWNTQQPEEKKAdlsrqhaRLNDVLEVLDVRLDGREFIAGDSFTAADVVLASILHLAHTLKL-LDGYPKL 179
Cdd:cd03177    30 FGGAEPPEEKLD-------KLEEALEFLETFLEGSDYVAGDQLTIADLSLVATVSTLEVVGFdLSKYPNV 92

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 1243038490 116 QPEEKKADLSRQHARLNDVLEVLDVRLDGREFIAGDSFTAADVVLASILHLAHTLK---LLDGYPKLFEYTLRQAKRP 190
Cdd:pfam00043  16 PEEKKEPEVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIALAPALLWLYELDpacLREKFPNLKAWFERVAARP 93

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1243038490 135 LEVLDVRLDGREFIAGDSFTAADVVLASIL---------HLAHTLKLLDGYPKLFEYTLRQAKRPATRRAVS 197
Cdd:cd03190    46 LDKLEKRLSKQPYLLGDRLTEADIRLFTTLirfdpvyhqHFKCNLKTIRDYPNLWRYLRRLYQNPGVFETTN 117

stringent starvation protein A; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1243038490  43 LALHPLGEVPVLVDGATVLFESLAICLHLADRFPEKKLAP 82
Cdd:PRK09481   51 IDLNPYQSVPTLVDRELTLYESRIIMEYLDERFPHPPLMP 90

Glutathione S-transferase C-terminal-like, alpha helical domain of vertebrate Valyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, Valyl-tRNA synthetase (ValRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of human ValRS and its homologs from other vertebrates such as frog and zebrafish. 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. They typically form large stable complexes with other proteins. 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. The GST_C-like domain of ValRS from higher eukaryotes is likely involved in protein-protein interactions, to mediate the formation of the multi-aaRS complex that acts as a molecular hub to coordinate protein synthesis. ValRSs from prokaryotes and lower eukaryotes, such as fungi and plants, do not appear to contain this GST_C-like domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1243038490  94 QWIVFAEVTLDP--------LVVEHYWNTQQPEEKKADLSRqharlndVLEVLDVRLDGREFIAGDSFTAADVVLASILH 165
Cdd:cd10294     7 QWVSFADNELTPaacaaafpLLGLSGSDKQNQQRSLAELQR-------VLKVLDCYLKLRTYLVGEAITLADIAVACALL 79

                          90       100
                  ....*....|....*....|....
gi 1243038490 166 LAhtlklldgypklFEYTLRQAKR 189
Cdd:cd10294    80 LP------------FKYVLDPARR 91

GST_N family, Class Tau 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. The plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1243038490  11 ATRARWLLEELEVPYELVKLDVAKqetTTPAHLALHPL-GEVPVLVDGATVLFESLAI 67
Cdd:cd03058    12 VLRVRIALALKGVPYEYVEEDLGN---KSELLLASNPVhKKIPVLLHNGKPICESLII 66