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 494958352   3 QLFQFPLCPFSRKVRLLLGEKGVGYDLVRESPWEGR-DEFLDLNPAGTTPVMVDqeKGVTLIDSQAICEYFE 73
Cdd:cd00570    2 KLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEqEEFLALNPLGKVPVLED--GGLVLTESLAILEYLA 71

stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 494958352   4 LFQFPLCPFSRKVRLLLGEKGVGYDLVRESPWEGRDEFLDLNPAGTTPVMVDQEkgVTLIDSQAICEYFEETVEKFPLIS 83
Cdd:PRK09481  13 LFSGPTDIYSHQVRIVLAEKGVSVEIEQVEKDNLPQDLIDLNPYQSVPTLVDRE--LTLYESRIIMEYLDERFPHPPLMP 90

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 494958352  84 GTAAGRAEVRRLTAFFDQNFYGdvvgplLHERMKKRLIERAPPDARVLREAM 135
Cdd:PRK09481  91 VYPVARGESRLMMHRIEKDWYS------LMNKIVNGSASEADAARKQLREEL 136

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 494958352   3 QLFQFPLCPFSRKVRLLLGEKGVGYDLVRESPWEGR-DEFLDLNPAGTTPVMVDqeKGVTLIDSQAICEYFE 73
Cdd:cd00570    2 KLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEqEEFLALNPLGKVPVLED--GGLVLTESLAILEYLA 71

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 494958352    4 LFQFPLCPFSRKVRLLLGEKGVGYDLVRESPWEGRDEFLDLNPAGTTPVMVDQekGVTLIDSQAICEYFEETVE 77
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPLGKVPVLEDD--GGILCESLAIIDYLEELYP 72

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 494958352   4 LFQFPLCPFSRKVRLLLGEKGVGYDLVRESPWEG---RDEFLDLNPAGTTPVMVdQEKGVTLIDSQAICEYFE 73
Cdd:cd03051    3 LYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGeqrSPEFLAKNPAGTVPVLE-LDDGTVITESVAICRYLE 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 494958352   3 QLFQFPLCPFSRKVRLLLGEKGVG--YDLVRESPWEGRDEFLDLNPAGTTPVMVdQEKGVTLIDSQAICEY 71
Cdd:cd03049    2 KLLYSPTSPYVRKVRVAAHETGLGddVELVLVNPWSDDESLLAVNPLGKIPALV-LDDGEALFDSRVICEY 71

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 494958352   8 PLCPFSRKVRLLLGEKGVGYDLVRESPWEGRD---EFLDLNPAGTTPVMVDQEkgVTLIDSQAICEYFEETV--EKFPLI 82
Cdd:PLN02395   8 PAFASPKRALVTLIEKGVEFETVPVDLMKGEHkqpEYLALQPFGVVPVIVDGD--YKIFESRAIMRYYAEKYrsQGPDLL 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 494958352  83 SGTAAGRAEVRRLTAFFDQNFYGDVVGPLLHERMKKRLieRAPPDARVLREAMKRANVHMDYMDYLLDHRAWMAGGTLSL 162
Cdd:PLN02395  86 GKTIEERGQVEQWLDVEATSYHPPLLNLTLHILFASKM--GFPADEKVIKESEEKLAKVLDVYEARLSKSKYLAGDFVSL 163

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 494958352 163 ADIaaaAHLSVADYLGGIDWAGH-----ETVKRWYAGFKSRPSFRPLLS 206
Cdd:PLN02395 164 ADL---AHLPFTEYLVGPIGKAYlikdrKHVSAWWDDISSRPAWKEVLA 209

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 494958352    4 LFQFPLCPFSRKVRLLLGEKGVGYDLVRESPWEGRD---EFLDLNPAGTTPVMVDQEKgvTLIDSQAICEYFEE 74
Cdd:pfam02798   5 LYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEkspELLKLNPLGKVPALEDGGK--KLTESRAILEYIAR 76

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 494958352   3 QLFQFPLCPFSRKVRLLLGEKGVGYDLVRESPWEG---RDEFLDLNPAGTTPVMVDQekGVTLIDSQAICEY 71
Cdd:cd03056    2 KLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKGetrTPEFLALNPNGEVPVLELD--GRVLAESNAILVY 71

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 494958352  10 CPFSRKVRLLLGEKGVGY-----DLVRESPWegrdeFLDLNPAGTTPVMVDQEKGVTliDSQAICEYFEETVEKFPLisG 84
Cdd:PLN02817  73 CPFCQRVLLTLEEKHLPYdmklvDLTNKPEW-----FLKISPEGKVPVVKLDEKWVA--DSDVITQALEEKYPDPPL--A 143

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 494958352  85 TAAGRAEVrrltaffDQNFYGDVVGpllhermkkRLIERAPPDA--RVLREAMKRANvhmdymDYLLDHRAWMAGGTLSL 162
Cdd:PLN02817 144 TPPEKASV-------GSKIFSTFIG---------FLKSKDPGDGteQALLDELTSFD------DYIKENGPFINGEKISA 201

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 494958352 163 ADIAAAA---HLSVAdyLGGI-DWAGHET---VKRWYAGFKSRPSFRPLLSERMEVI 212
Cdd:PLN02817 202 ADLSLGPklyHLEIA--LGHYkNWSVPDSlpfVKSYMKNIFSMESFVKTRALPEDVI 256

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 494958352   4 LFQFPLCPFSRKVRLLLGEKGVGYDLVRESPWEG---RDEFLDLNPAGTTPVMVDQekGVTLIDSQAICEY 71
Cdd:cd03045    3 LYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKGehlKPEFLKLNPQHTVPTLVDN--GFVLWESHAILIY 71

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 494958352  89 RAEV-RRLtaFFD-----QNFYgDVVGPLLHERmkkrlierAPPDARVLrEAMKRAnvhMDYMDYLLDHRAWMAGGTLSL 162
Cdd:cd03177    3 RAIVnQRL--FFDsgtlyQRLR-DYYYPILFGG--------AEPPEEKL-DKLEEA---LEFLETFLEGSDYVAGDQLTI 67

                         90       100       110
                 ....*....|....*....|....*....|.
gi 494958352 163 ADIAAAAHLSVADYLgGIDWAGHETVKRWYA 193
Cdd:cd03177   68 ADLSLVATVSTLEVV-GFDLSKYPNVAAWYE 97

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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 494958352  18 LLLGEKGVGYD--LVRESPWEGRDEFLDLNPAGTTPVMVDqeKGVTLIDSQAICEY 71
Cdd:cd03043   18 LLLKAAGIPFEeiLVPLYTPDTRARILEFSPTGKVPVLVD--GGIVVWDSLAICEY 71

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 494958352 123 RAPPDARV---LREAMKRANVHMDYMDYLLDHRAWMAGGTLSLADIAAAahLSVADYLG-GIDWAGHETVKRWYAGFKSR 198
Cdd:cd03180   30 RTPPEQRDpaaIAASLAACNKLMAILDAQLARQAYLAGDRFTLADIALG--CSVYRWLElPIERPALPHLERWYARLSQR 107

                 ...
gi 494958352 199 PSF 201
Cdd:cd03180  108 PAF 110

C-terminal, alpha helical domain of an unknown subfamily 6 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 6; composed of uncharacterized bacterial proteins with similarity to GSTs, including Pseudomonas fluorescens GST with a known three-dimensional structure. 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. Though the three-dimensional structure of Pseudomonas fluorescens GST has been determined, there is no information on its functional characterization.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 494958352 157 GGTLSLADIAAAAHLSVADY-LGGIDW-AGHETVKRWYAGFKSRPSFR 202
Cdd:cd03205   58 GGRLTLGDIAVACALGYLDFrFPELDWrAGHPALAAWFARFEARPSFQ 105

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 494958352  10 CPfsRKVRLLLGEKGVGYDLVR---ESPWEGRDEFLDLNPAGTTPVMVDQEkgVTLIDSQAICEYFeetVEKFP-----L 81
Cdd:PLN02473  13 NP--QRVLLCFLEKGIEFEVIHvdlDKLEQKKPEHLLRQPFGQVPAIEDGD--LKLFESRAIARYY---ATKYAdqgtdL 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 494958352  82 ISGTAAGRAEVRRLtAFFDQNFYGDVVGPL-LHERMKKRLIEraPPDARVLREAMKRANVHMDYMDYLLDHRAWMAGGTL 160
Cdd:PLN02473  86 LGKTLEHRAIVDQW-VEVENNYFYAVALPLvINLVFKPRLGE--PCDVALVEELKVKFDKVLDVYENRLATNRYLGGDEF 162

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 494958352 161 SLADIAaaaHLSVADYLGGI-DWAG----HETVKRWYAGFKSRPSFRPLL 205
Cdd:PLN02473 163 TLADLT---HMPGMRYIMNEtSLSGlvtsRENLNRWWNEISARPAWKKLM 209

glutathione S-transferase DHAR1

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 494958352  10 CPFSRKVRLLLGEKGVGYDLVRESPWEGRDEFLDLNPAGTTPVMVDQEKGVTliDSQAICEYFEETVEKFPL 81
Cdd:PLN02378  20 CPFSQRALLTLEEKSLTYKIHLINLSDKPQWFLDISPQGKVPVLKIDDKWVT--DSDVIVGILEEKYPDPPL 89

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 494958352  14 RKVRLLLGEKGVGYDLVresPWEGR------DEFLDLNPAGTTPVMVDQEkgVTLIDSQAICEY 71
Cdd:cd03047   13 QKVLWLLDELGLPYERI---DAGGQfggldtPEFLAMNPNGRVPVLEDGD--FVLWESNAILRY 71

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
                 ....*....|....*....|....*....|....
gi 494958352  39 DEFLDLNPAGTTPVMVDqEKGVTLIDSQAICEYF 72
Cdd:cd03044   40 PEFLKKFPLGKVPAFEG-ADGFCLFESNAIAYYV 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 494958352 125 PPDARVLREAMKRANVHMDYM-DYLLDHRAWMAGGTLSLADIAAAAHLSVADYLGGIDWAGHETVKRWYAGFKSR 198
Cdd:cd03183   37 PVSPEKVKKAEENLEESLDLLeNKFLKDKPFLAGDEISIADLSAICEIMQPEAAGYDVFEGRPKLAAWRKRVKEA 111

C-terminal, alpha helical domain of an unknown subfamily 9 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 9; 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 494958352  92 VRRLtafFDQNFYGDVVGPLLHERMKKRLIERAPPDARVLReamkranvhmdymdylldHRAWMAGGTLSLADIAAAAHL 171
Cdd:cd10424   16 ARRL---YPEAFFGGKVSPEIKEEVRKDLLRGIAALARLAR------------------FAPYVAGETFTLADCAAFVHL 74

                         90
                 ....*....|....
gi 494958352 172 SVADYLG----GID 181
Cdd:cd10424   75 PLVALATkkfyGED 88

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 494958352  87 AGRAEVRRLTAFFDQNFYGDVVGPLLHERMkkrLIERAPPDAR-VLREAMKRanvHMDYMDYLLDHRAWMAGGTLSLADI 165
Cdd:cd03188    1 LERARLLEWLNFIASELHKAFGPLFYPARW---ADDALAEEVKaAARERLER---RLAYLDAQLAGGPYLLGDQFSVADA 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 494958352 166 AAAAHLSVADYLgGIDWAGHETVKRWYAGFKSRPSFRPLL 205
Cdd:cd03188   75 YLFVVLRWARAV-GLDLSDWPHLAAYLARVAARPAVQAAL 113