glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001   1 MKLYCKPGACSLSPHIVALECGLDFTQVNVDLQKKVTEQGEDYWQINPKGQVPALQFDDGSILTEGVAIVQYLADLKPDR 80
Cdd:PRK10542    1 MKLFYKPGACSLASHITLRESGLDFTLVSVDLAKKRLENGDDYLAINPKGQVPALLLDDGTLLTEGVAIMQYLADSVPDR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001  81 NLLAPTGSLTRYHTLEWLSYVSSELHKGFSPLFRPDTPEEYKAIARAQLEKKYQQVNEALQDKQWLLGLRFTVADVYLFV 160
Cdd:PRK10542   81 QLLAPVGSLSRYHTIEWLNYIATELHKGFTPLFRPDTPEEYKPTVRAQLEKKFQYVDEALADEQWICGQRFTIADAYLFT 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1860023001 161 VTRWAKAIKLDLSGLDALEAWFSRVAERPAVQAALKAEGL 200
Cdd:PRK10542  161 VLRWAYAVKLNLEGLEHIAAYMQRVAERPAVAAALKAEGL 200

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001   1 MKLYCKPGACSLSPHIVALECGLDFTQVNVDLQKKVTEQGEDYWQINPKGQVPALQFDDGSILTEGVAIVQYLADLKPDR 80
Cdd:PRK10542    1 MKLFYKPGACSLASHITLRESGLDFTLVSVDLAKKRLENGDDYLAINPKGQVPALLLDDGTLLTEGVAIMQYLADSVPDR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001  81 NLLAPTGSLTRYHTLEWLSYVSSELHKGFSPLFRPDTPEEYKAIARAQLEKKYQQVNEALQDKQWLLGLRFTVADVYLFV 160
Cdd:PRK10542   81 QLLAPVGSLSRYHTIEWLNYIATELHKGFTPLFRPDTPEEYKPTVRAQLEKKFQYVDEALADEQWICGQRFTIADAYLFT 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1860023001 161 VTRWAKAIKLDLSGLDALEAWFSRVAERPAVQAALKAEGL 200
Cdd:PRK10542  161 VLRWAYAVKLNLEGLEHIAAYMQRVAERPAVAAALKAEGL 200

C-terminal, alpha helical domain of Class Beta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Beta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they are involved in the protection against oxidative stress and are able to bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs, contributing to antibiotic resistance. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH. One member of this subfamily is a GST from Burkholderia xenovorans LB400 that is encoded by the bphK gene and is part of the biphenyl catabolic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001  89 LTRYHTLEWLSYVSSELHKGFSPLFRPDTP------EEYKAIARAQLEKKYQQVNEALQDKQWLLGLRFTVADVYLFVVT 162
Cdd:cd03188     1 LERARLLEWLNFIASELHKAFGPLFYPARWaddalaEEVKAAARERLERRLAYLDAQLAGGPYLLGDQFSVADAYLFVVL 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1860023001 163 RWAKAIKLDLSGLDALEAWFSRVAERPAVQAAL 195
Cdd:cd03188    81 RWARAVGLDLSDWPHLAAYLARVAARPAVQAAL 113

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001   1 MKLYCKPGACSLSPHIVALECGLDFTQVNVDLQKKVTEQGEDYWQINPKGQVPALQFDDGSILTEGVAIVQYLADLKPDR 80
Cdd:PRK10542    1 MKLFYKPGACSLASHITLRESGLDFTLVSVDLAKKRLENGDDYLAINPKGQVPALLLDDGTLLTEGVAIMQYLADSVPDR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001  81 NLLAPTGSLTRYHTLEWLSYVSSELHKGFSPLFRPDTPEEYKAIARAQLEKKYQQVNEALQDKQWLLGLRFTVADVYLFV 160
Cdd:PRK10542   81 QLLAPVGSLSRYHTIEWLNYIATELHKGFTPLFRPDTPEEYKPTVRAQLEKKFQYVDEALADEQWICGQRFTIADAYLFT 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1860023001 161 VTRWAKAIKLDLSGLDALEAWFSRVAERPAVQAALKAEGL 200
Cdd:PRK10542  161 VLRWAYAVKLNLEGLEHIAAYMQRVAERPAVAAALKAEGL 200

C-terminal, alpha helical domain of Class Beta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Beta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they are involved in the protection against oxidative stress and are able to bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs, contributing to antibiotic resistance. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH. One member of this subfamily is a GST from Burkholderia xenovorans LB400 that is encoded by the bphK gene and is part of the biphenyl catabolic pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001  89 LTRYHTLEWLSYVSSELHKGFSPLFRPDTP------EEYKAIARAQLEKKYQQVNEALQDKQWLLGLRFTVADVYLFVVT 162
Cdd:cd03188     1 LERARLLEWLNFIASELHKAFGPLFYPARWaddalaEEVKAAARERLERRLAYLDAQLAGGPYLLGDQFSVADAYLFVVL 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1860023001 163 RWAKAIKLDLSGLDALEAWFSRVAERPAVQAAL 195
Cdd:cd03188    81 RWARAVGLDLSDWPHLAAYLARVAARPAVQAAL 113

Glutathione S-transferase (GST) family, N-terminal domain; a large, diverse group of cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK subfamily, a member of the DsbA family). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxin 2 and stringent starvation protein A.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1860023001   1 MKLYCKPG-ACSLSPHIVALECGLDFTQVNVDLQKKvteQGEDYWQINPKGQVPALQfDDGSILTEGVAIVQYLA 74
Cdd:cd00570     1 LKLYYFPGsPRSLRVRLALEEKGLPYELVPVDLGEG---EQEEFLALNPLGKVPVLE-DGGLVLTESLAILEYLA 71

GSH-dependent disulfide bond oxidoreductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001  20 ECGLDFTQVNVDLQKKVTEQGEdYWQINPKGQVPAL----QFDDGSILT--EGVAIVQYLADlkpDRNLLAPTGSLTRYH 93
Cdd:PRK13972   21 EAELDYRLIKVDLGKGGQFRPE-FLRISPNNKIPAIvdhsPADGGEPLSlfESGAILLYLAE---KTGLFLSHETRERAA 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001  94 TLEWLSYVSSelhkGFSPL------FRPDTPEEYK-AIARAQLEKK--YQQVNEALQDKQWLLGLRFTVADVYLFV-VTR 163
Cdd:PRK13972   97 TLQWLFWQVG----GLGPMlgqnhhFNHAAPQTIPyAIERYQVETQrlYHVLNKRLENSPWLGGENYSIADIACWPwVNA 172

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1860023001 164 WAKAiKLDLSGLDALEAWFSRVAERPAVQAAL 195
Cdd:PRK13972  173 WTRQ-RIDLAMYPAVKNWHERIRSRPATGQAL 203

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 1860023001   1 MKLYckpgACSLSPH-----IVALECGLDFTQVNVDLQKKvtEQ-GEDYWQINPKGQVPALQFDDGSILTEGVAIVQYL 73
Cdd:cd03051     1 MKLY----DSPTAPNprrvrIFLAEKGIDVPLVTVDLAAG--EQrSPEFLAKNPAGTVPVLELDDGTVITESVAICRYL 73

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1860023001   1 MKLYCKPGACSLSPHIVALECGLDFTQVNVDLQKKVTEQgEDYWQINPKGQVPALQfDDGSILTEGVAIVQYLADL 76
Cdd:cd03046     1 ITLYHLPRSRSFRILWLLEELGLPYELVLYDRGPGEQAP-PEYLAINPLGKVPVLV-DGDLVLTESAAIILYLAEK 74

C-terminal, alpha helical domain of an unknown subfamily 2 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 2; composed of uncharacterized bacterial proteins, with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001  97 WLSYVSSELHKGFSPLF----RpdTPEEYK---AIAR--AQLEKKYQQVNEALQDKQWLLGLRFTVADVYLFVVT-RWaK 166
Cdd:cd03180     9 WMDWQTSTLNPAFRYAFwglvR--TPPEQRdpaAIAAslAACNKLMAILDAQLARQAYLAGDRFTLADIALGCSVyRW-L 85

                          90       100
                  ....*....|....*....|....
gi 1860023001 167 AIKLDLSGLDALEAWFSRVAERPA 190
Cdd:cd03180    86 ELPIERPALPHLERWYARLSQRPA 109

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 1860023001   1 MKLYCKPGAC-SLSPHIVALECGLDFTQVNVDLQKKvTEQGEDYWQINPKGQVPALQfDDGSILTEGVAIVQYLAD 75
Cdd:pfam02798   3 LTLYGIRGSPrAHRIRWLLAEKGVEYEIVPLDFGAG-PEKSPELLKLNPLGKVPALE-DGGKKLTESRAILEYIAR 76

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 1860023001   1 MKLYCKPG-ACSLSPHIVALECGLDFTQVNVDLQKKVTEQgEDYWQINPKGQVPALQfDDGSILTEGVAIVQYLAD 75
Cdd:cd03053     2 LKLYGAAMsTCVRRVLLCLEEKGVDYELVPVDLTKGEHKS-PEHLARNPFGQIPALE-DGDLKLFESRAITRYLAE 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 1860023001  96 EWLSYVSSELHKGFSPL-----FRPDTPEEYKAIARAQLEKKYQQVNEALQDKQWLLGLRFTVADVYLFVVTRWAKAIKL 170
Cdd:cd00299     3 ALEDWADATLAPPLVRLlylekVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEALGP 82

                          90
                  ....*....|....*...
gi 1860023001 171 DLSGLD---ALEAWFSRV 185
Cdd:cd00299    83 YYDLLDeypRLKAWYDRL 100

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1860023001  15 HIVALECGLDFTQVNVDLQKKvtEQ-GEDYWQINPKGQVPALQfDDGSILTEGVAIVQYLAD 75
Cdd:cd03050    16 YIFLKLNKIPFEECPIDLRKG--EQlTPEFKKINPFGKVPAIV-DGDFTLAESVAILRYLAR 74

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001 111 PLFRPDTPEEYKAIARAQLEK--KYQQV-NEALQDKQWLLGLRFTVADVYLFVVTRWAKAIKLDL-SGLDALEAWFSRVA 186
Cdd:cd03182    32 PGLKPDREVQVPEWGERNKKRviDFLPVlDKRLAESPYVAGDRFSIADITAFVALDFAKNLKLPVpEELTALRRWYERMA 111

                  ....*
gi 1860023001 187 ERPAV 191
Cdd:cd03182   112 ARPSA 116

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001   1 MKLYCKPgacsLSPH-----IVALECGL--DFTQVNVDlqkkVTEQGEDYWQINPKGQVPALQFDDGSILTEGVAIVQYL 73
Cdd:cd03049     1 MKLLYSP----TSPYvrkvrVAAHETGLgdDVELVLVN----PWSDDESLLAVNPLGKIPALVLDDGEALFDSRVICEYL 72

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 1860023001  95 LEWLSYVSSELHKGFSPLFRP------DTPEEYKAiARAQLEKKYQQVNEALQDKQWLLGLRFTVADVYLFVVTRWAKAI 168
Cdd:cd03181     6 LQWISFANSELLPAAATWVLPllgiapYNKKAVDK-AKEDLKRALGVLEEHLLTRTYLVGERITLADIFVASALLRGFET 84

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1860023001 169 KLDLSGLD---ALEAWFSRVAERPAVQAALK 196
Cdd:cd03181    85 VLDPEFRKkypNVTRWFNTVVNQPKFKAVFG 115

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001 105 LHKGFSPLFRPDTPEE---YKAIARAQLEKKYQQVNEALQDKQ--WLLGLRFTVADVYLFVV---TRWAKAIKLdLSGLD 176
Cdd:pfam14497   4 HHPIASSLYYEDEKKKakrRKEFREERLPKFLGYFEKVLNKNGggYLVGDKLTYADLALFQVldgLLYPKAPDA-LDKYP 82

                          90       100
                  ....*....|....*....|..
gi 1860023001 177 ALEAWFSRVAERPAVQAALKAE 198
Cdd:pfam14497  83 KLKALHERVAARPNIKAYLASR 104

GST_N family, Class Omega 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 Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1860023001  15 HIVALECGLDFTQVNVDLQKKVteqgEDYWQINPKGQVPALQFDDGSILTEGVAIVQYL 73
Cdd:cd03055    34 RLVLAAKNIPHEVININLKDKP----DWFLEKNPQGKVPALEIDEGKVVYESLIICEYL 88

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1860023001 125 ARAQLEKKYQQVNEALQDKQWLLGLRFTVADVYLFVVTRWAKAIKLDL---SGLDALEAWFSR 184
Cdd:pfam13410   5 AREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPGLdlrEGYPRLRAWLER 67

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 1860023001  20 ECGLDFTQVNVDLQKKVTeQGEDYWQINPKGQVPALQfDDGSILTEGVAIVQYLA 74
Cdd:cd03047    21 ELGLPYERIDAGGQFGGL-DTPEFLAMNPNGRVPVLE-DGDFVLWESNAILRYLA 73

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001 105 LHKGFSPLF--RPDTPEEYKAiARAQLEKKYQQV-NEALQDKQWLLGLRFTVADVYLFVVTRWAKAIKLD-LSGLDALEA 180
Cdd:cd03183    25 WQKVLLPLFggTPVSPEKVKK-AEENLEESLDLLeNKFLKDKPFLAGDEISIADLSAICEIMQPEAAGYDvFEGRPKLAA 103

                  ....*...
gi 1860023001 181 WFSRVAER 188
Cdd:cd03183   104 WRKRVKEA 111

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1860023001   1 MKLYCKPgACSLSpH---IVALECGLDFTQVNVDLQKKvteqGEDYWQINPKGQVPALqFDDGSILTEGVAIVQYL 73
Cdd:cd03059     1 MTLYSGP-DDVYS-HrvrIVLAEKGVSVEIIDVDPDNP----PEDLAELNPYGTVPTL-VDRDLVLYESRIIMEYL 69

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001  91 RYHTLEWLSYVSSE---LHKGFSPlFRPDTPEEYK-AIARAQLEKKYQQ--VNEALQDKQWLLGLRFTVADVYLF----- 159
Cdd:cd10292     2 RTETLNWLFWQMGSapyLGGGFGH-FYSYAPVKIEyAIDRFTMEAKRQLdvLDRQLATHKYLAGDEYTIADMAIWpwygg 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1860023001 160 VVTRWA--KAIKLDLSGLDALEAWFSRVAERPAVQ 192
Cdd:cd10292    81 LALGSLydAAEFLDVDEYKHVQRWAKDIAARPAVK 115

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1860023001 101 VSSELHKGFSPL--------FRPDTPEEYKAIARAQLEKKYQQVNEALQ----DKQWLLGlRFTVADV-YLFVVTRWaKA 167
Cdd:cd03194    10 ACAEMHSGFSALrsacpmnlRARRPGVELSPAVQADIARIEAIWTEARArfgaGGPFLFG-EFSIADAfYAPVVTRF-RT 87

                          90       100       110
                  ....*....|....*....|....*....|
gi 1860023001 168 IKLDLSGldALEAWFSRVAERPAVQAALKA 197
Cdd:cd03194    88 YGVPLSP--AARAYVEALLALPAMQEWIEA 115