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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811   1 MIDLYYA-PTPNGHKITLFLEEAELAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVDhmpaDGgapLSVFESGAILLYL 79
Cdd:COG0625    1 MMKLYGSpPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVD----DG---LVLTESLAILEYL 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811  80 AEKSG--KLLSGELRERYVTLQWLFWQVGGLGPMLGQnqHFSHSAPQTVPYAIERFQVETQRLYGVLNQRLGCSPWLGGD 157
Cdd:COG0625   74 AERYPepPLLPADPAARARVRQWLAWADGDLHPALRN--LLERLAPEKDPAAIARARAELARLLAVLEARLAGGPYLAGD 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 839495811 158 HYSIADIAAWPWVNCHVRQRIDLANYPAVHNWYERIKQRPATSEAM 203
Cdd:COG0625  152 RFSIADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAFQRAL 197

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 839495811    8 PTPNGHKITLFLEEAELAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVDHmpadggaPLSVFESGAILLYLAE 81
Cdd:pfam02798  10 GSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDG-------GKKLTESRAILEYIAR 76

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811   1 MIDLYYA-PTPNGHKITLFLEEAELAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVDhmpaDGgapLSVFESGAILLYL 79
Cdd:COG0625    1 MMKLYGSpPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVD----DG---LVLTESLAILEYL 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811  80 AEKSG--KLLSGELRERYVTLQWLFWQVGGLGPMLGQnqHFSHSAPQTVPYAIERFQVETQRLYGVLNQRLGCSPWLGGD 157
Cdd:COG0625   74 AERYPepPLLPADPAARARVRQWLAWADGDLHPALRN--LLERLAPEKDPAAIARARAELARLLAVLEARLAGGPYLAGD 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 839495811 158 HYSIADIAAWPWVNCHVRQRIDLANYPAVHNWYERIKQRPATSEAM 203
Cdd:COG0625  152 RFSIADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAFQRAL 197

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811  93 ERYVTLQWLFWQVGGLGPMLGQNQHFSHSAPQTVPYAIERFQVETQRLYGVLNQRLGCSPWLGGDHYSIADIAAWPWVNC 172
Cdd:cd10291    1 ERYAVLQWLMWQMGGLGPMQGQAHHFKRYAPEKIPYAIKRYTNETKRLYGVLDRRLAKSKYLAGDEYSIADIAIWPWVAR 80

                         90       100
                 ....*....|....*....|....*..
gi 839495811 173 HVRQRIDLANYPAVHNWYERIKQRPAT 199
Cdd:cd10291   81 HEWQGIDLADFPNLKRWFERLAARPAV 107

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 839495811   1 MIDLYYAPTPNGHKITLFLEEAELAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVDHmpadGGAPLSVFESGAILLYLA 80
Cdd:cd03048    1 MITLYTHGTPNGFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDH----NGTPLTVFESGAILLYLA 76

                 ....*
gi 839495811  81 EKSGK 85
Cdd:cd03048   77 EKYDK 81

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811  93 ERYVTLQWLFWQVGGLGPMLGQNQHFSHSAPQTVPYAIERFQVETQRLYGVLNQRLGCS--PWLGGDHYSIADIAAWPWV 170
Cdd:cd10293    1 EYYQAKQWLFFQASGQGPYWGQAGWFNVFHAEKVPSAIERYTNEIRRVLGVLETALAERyrVWLVGDKFTIADLAFVPWN 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 839495811 171 NchVRQRI-------DLANYPAVHNWYERIKQRPATSEA 202
Cdd:cd10293   81 N--VVDMIfidpeldIKKEFPHVYKWLKRMLARPAVKKA 117

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811   2 IDLYYAPT-PNGHKITLFLEEAELAYRLIRVDIGKGEqfHPQFLAISPNNKVPAIVDHmpadggaPLSVFESGAILLYLA 80
Cdd:cd00570    1 LKLYYFPGsPRSLRVRLALEEKGLPYELVPVDLGEGE--QEEFLALNPLGKVPVLEDG-------GLVLTESLAILEYLA 71

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        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 839495811   4 LY-YAPTPNGHKITLFLEEAELAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVdhmpaDGGAPLSvfESGAILLYLA 80
Cdd:cd03056    3 LYgFPLSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLALNPNGEVPVLE-----LDGRVLA--ESNAILVYLA 73

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811   4 LY-YAPTPNGHKITLFLEEAELAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVDHmpadggaPLSVFESGAILLYLAEK 82
Cdd:cd03053    4 LYgAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDG-------DLKLFESRAITRYLAEK 76

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811  11 NGHKITLFLEEAELAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVDhmpadggAPLSVFESGAILLYLAEKSG----KL 86
Cdd:PLN02473  13 NPQRVLLCFLEKGIEFEVIHVDLDKLEQKKPEHLLRQPFGQVPAIED-------GDLKLFESRAIARYYATKYAdqgtDL 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811  87 LSGELRERYVTLQWL---FWQVGGLGPMLGQNQHFSHSAPQTVPYA-IERFQVETQRLYGVLNQRLGCSPWLGGDHYSIA 162
Cdd:PLN02473  86 LGKTLEHRAIVDQWVeveNNYFYAVALPLVINLVFKPRLGEPCDVAlVEELKVKFDKVLDVYENRLATNRYLGGDEFTLA 165

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 839495811 163 DIAAWPWVNcHVRQRIDLANY----PAVHNWYERIKQRPATSEAM 203
Cdd:PLN02473 166 DLTHMPGMR-YIMNETSLSGLvtsrENLNRWWNEISARPAWKKLM 209

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 839495811   4 LYYAPTPNGHKITLFLEEAELAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVDhmpaDGGAPLsvFESGAILLYLAEK 82
Cdd:cd03057    3 LYYSPGACSLAPHIALEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVL----DDGEVL--TESAAILQYLADL 75

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 839495811  99 QWLFWQVGGLGPMLGQNQHFSHSAPQTVPYAIERFQVETQRLYGVLNQRLGCSPWLGGDHYSIADIAAWPWVNCHVR--- 175
Cdd:cd00299    3 ALEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEAlgp 82

                         90
                 ....*....|....*...
gi 839495811 176 QRIDLANYPAVHNWYERI 193
Cdd:cd00299   83 YYDLLDEYPRLKAWYDRL 100

C-terminal, alpha helical domain of an unknown subfamily 5 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 5; composed of uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 839495811 144 LNQRLGCSPWLGGDHYSIADIAAWPWVN--CHV-RQRIDLANYPAVHNWYERIKQRPATSEAM 203
Cdd:cd03196   53 LEARLSQHAYLFGDRPSLADYAIFPFVRqfAHVdRDWFDASPYPNLRRWLNRFLQSPLFSKIM 115

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 839495811 141 YGVLNQRLGCSPWLGGDHYSIADIAAWPWVNCHVRQRIDLANYPAVHNWYERIKQRPATSEAMLK 205
Cdd:cd03177   47 LEFLETFLEGSDYVAGDQLTIADLSLVATVSTLEVVGFDLSKYPNVAAWYERLKALPPGEEENGE 111

C-terminal, alpha helical domain of GTT2-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the Saccharomyces cerevisiae GST protein, GTT2. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. GTT2, a homodimer, exhibits GST activity with standard substrates. Strains with deleted GTT2 genes are viable but exhibit increased sensitivity to heat shock.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 839495811 143 VLNQRLGCSPWLGGDHYSIADIAAWPWVN--CHVRQRIDLANyPAVHNWYERIKQRPA 198
Cdd:cd03182   59 VLDKRLAESPYVAGDRFSIADITAFVALDfaKNLKLPVPEEL-TALRRWYERMAARPS 115

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 839495811   4 LY-YAPTPNGHKITLFLEEAELAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVdhmpADGGAPLSvfESGAILLYL 79
Cdd:cd03051    3 LYdSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLE----LDDGTVIT--ESVAICRYL 73

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 839495811  11 NGHKITLFLEEAELAYRliRVDIGK--GEQFHPQFLAISPNNKVPAIVdhmpaDGGAPLsvFESGAILLYLA 80
Cdd:cd03047   11 NVQKVLWLLDELGLPYE--RIDAGGqfGGLDTPEFLAMNPNGRVPVLE-----DGDFVL--WESNAILRYLA 73

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 839495811  24 LAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVdhmpaDGGAPLSvfESGAILLYL 79
Cdd:cd03042   24 LDYEYVPVNLLKGEQLSPAYRALNPQGLVPTLV-----IDGLVLT--QSLAIIEYL 72

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 839495811  92 RERYvtLQWLFWQVGGLGPMLGQNQHFSHSAPQTVPYAIE------------RFQVETQRLYGVLNQRLGCSPWLGGDHY 159
Cdd:cd03189    8 YADY--LYWLHFAEGSLMPPLLLKLVFGKIGEAPPPFFRPisrkiadkplqaFINPELKRHLDFLEDHLAKHPYFAGDEL 85

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 839495811 160 SIADIAAWPWVNCHVRQRIDLANYPAVHNWYERIKQRP 197
Cdd:cd03189   86 TAADIMMSFPLEAALARGPLLEQYPNIAAYLERIEARP 123

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811    4 LYYAPT-PNGHKITLFLEEAELAYRLirVDIGKGEQFhPQFLAISPNNKVPAIVDhmpaDGGaplSVFESGAILLYLAEK 82
Cdd:pfam13417   1 LYGFPGsPYARRVRIALNEKGLPYEF--VPIPPGDHP-PELLAKNPLGKVPVLED----DGG---ILCESLAIIDYLEEL 70

                  ..
gi 839495811   83 SG 84
Cdd:pfam13417  71 YP 72

glutathione transferase;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 839495811  19 LEEAELAYRLIRVDIGKGEQFHPQFLAISPNNKVPAIVdhmpaDGGAPLSvfESGAILLYLAE 81
Cdd:PRK15113  26 LQEKGLPFELKTVDLDAGEHLQPTYQGYSLTRRVPTLQ-----HDDFELS--ESSAIAEYLEE 81

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 839495811 144 LNQRLGCSPWLGGDHYSIADIAAWPWV-----------NCHVRQridLANYPAVHNWYERIKQRPATSE 201
Cdd:cd03190   49 LEKRLSKQPYLLGDRLTEADIRLFTTLirfdpvyhqhfKCNLKT---IRDYPNLWRYLRRLYQNPGVFE 114

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 839495811 127 PYAIERFQVETQRLYGVLNQRLGCSPWLGGDHYSIADIAA-----WPWvnchvRQRID---LANYPAVHNWYERIKQRPA 198
Cdd:cd03181   35 KKAVDKAKEDLKRALGVLEEHLLTRTYLVGERITLADIFVasallRGF-----ETVLDpefRKKYPNVTRWFNTVVNQPK 109

                         90
                 ....*....|
gi 839495811 199 TSEAMLKIQL 208
Cdd:cd03181  110 FKAVFGEVKL 119

GST_N family, 2 repeats of the N-terminal domain of soluble GSTs (2 GST_N) subfamily; composed of uncharacterized 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 fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 839495811   1 MIDLY-YAPTPNGHKITLFLEEAELAYRLIrvDIGKGEQFHPQFLAISPNNKVPAIVDhmPADGgapLSVFESGAILLYL 79
Cdd:cd03041    1 PLELYeFEGSPFCRLVREVLTELELDVILY--PCPKGSPKRDKFLEKGGKVQVPYLVD--PNTG---VQMFESADIVKYL 73

                 ...
gi 839495811  80 AEK 82
Cdd:cd03041   74 FKT 76

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
                 ....*....|....*....|....*....|....*....|..
gi 839495811  41 PQFLAISPNNKVPAIVDhmpADGGaplSVFESGAILLYLAEK 82
Cdd:cd03044   40 PEFLKKFPLGKVPAFEG---ADGF---CLFESNAIAYYVANL 75