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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1754571039  91 ALRLTGLALAACEKSVQLVYERELRPSEKRHSPWTDRVRTQLHAAFQALELELAQVPlvatPDQIGEHGVTVAVAWRFHQ 170
Cdd:cd03205     1 ALRLEALADGICDAAVLIVYERRLRPEEKQHQPWIERQWGKIERALDALEAELGDLP----GGRLTLGDIAVACALGYLD 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1754571039 171 LMLPEIDFGDQFPELANFSAQAEALPAFLETPP 203
Cdd:cd03205    77 FRFPELDWRAGHPALAAWFARFEARPSFQATPP 109

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1754571039  91 ALRLTGLALAACEKSVQLVYERELRPSEKRHSPWTDRVRTQLHAAFQALELELAQVPlvatPDQIGEHGVTVAVAWRFHQ 170
Cdd:cd03205     1 ALRLEALADGICDAAVLIVYERRLRPEEKQHQPWIERQWGKIERALDALEAELGDLP----GGRLTLGDIAVACALGYLD 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1754571039 171 LMLPEIDFGDQFPELANFSAQAEALPAFLETPP 203
Cdd:cd03205    77 FRFPELDWRAGHPALAAWFARFEARPSFQATPP 109

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1754571039   3 LIGMLDSPYVRRVAICLKLLGLPYEHRSLSVFRTFDEFSAINPVVKAPTLVaDDGTVLMDSTLILQYLESLVDAER 78
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPLGKVPVLE-DDGGILCESLAIIDYLEELYPGPP 75

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 1754571039   1 MQLIGMLDSPYVRRVAICLKLLGLPYEHRSLSVF-RTFDEFSAINPVVKAPTLVaDDGTVLMDSTLILQYLE 71
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGeGEQEEFLALNPLGKVPVLE-DGGLVLTESLAILEYLA 71

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1754571039  91 ALRLTGLALAACEKSVQLVYERELRPSEKRHSPWTDRVRTQLHAAFQALELELAQVPlvatPDQIGEHGVTVAVAWRFHQ 170
Cdd:cd03205     1 ALRLEALADGICDAAVLIVYERRLRPEEKQHQPWIERQWGKIERALDALEAELGDLP----GGRLTLGDIAVACALGYLD 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1754571039 171 LMLPEIDFGDQFPELANFSAQAEALPAFLETPP 203
Cdd:cd03205    77 FRFPELDWRAGHPALAAWFARFEARPSFQATPP 109

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1754571039   3 LIGMLDSPYVRRVAICLKLLGLPYEHRSLSVFRTFDEFSAINPVVKAPTLVaDDGTVLMDSTLILQYLESLVDAER 78
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPLGKVPVLE-DDGGILCESLAIIDYLEELYPGPP 75

Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1754571039   9 SPYVRRVAICLKLLGLPYEHRSLSV--FRTFDEFSAINPVVKAPTLVADDGTVLMDSTLILQYLESL 73
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELVDLdpKDKPPELLALNPLGTVPVLVLPDGTVLTDSLVILEYLEEL 68

maleylacetoacetate isomerase; Maleylacetoacetate isomerase is an enzyme of tyrosine and phenylalanine catabolism. It requires glutathione and belongs by homology to the zeta family of glutathione S-transferases. The enzyme (EC 5.2.1.2) is described as active also on maleylpyruvate, and the example from a Ralstonia sp. catabolic plasmid is described as a maleylpyruvate isomerase involved in gentisate catabolism. [Energy metabolism, Amino acids and amines]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1754571039  14 RVAICLKLLGLPYEHRSLSVFRTF----DEFSAINPVVKAPTLVaDDGTVLMDSTLILQYLESlVDAERRLVPMAPEARL 89
Cdd:TIGR01262  13 RVRIALALKGIDYEYVPVNLLRDGeqrsPEFLALNPQGLVPTLD-IDGEVLTQSLAIIEYLEE-TYPDPPLLPADPIKRA 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1754571039  90 RALRLTglALAACE------KSVQLVYERELRPSEKRHSPWTDRVRTQLHAAFQAL------------ELELAQVPLVAt 151
Cdd:TIGR01262  91 RVRALA--LLIACDihplnnLRVLQYLREKLGVEEEARNRWYQHWISKGFAALEALlqphagrfcvgdTPTLADLCLVP- 167

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1754571039 152 pdqigehgvTVAVAWRFHQLMlpeidfgDQFPELANFSAQAEALPAFLETPP 203
Cdd:TIGR01262 168 ---------QVYNAERFGVDL-------TPYPTLRRIAAALAALPAFQRAHP 203

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 1754571039   1 MQLIGMLDSPYVRRVAICLKLLGLPYEHRSLSVFR---TFDEFSAINPVVKAPTLVaDDGTVLMDSTLILQYL 70
Cdd:cd03045     1 IDLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKgehLKPEFLKLNPQHTVPTLV-DNGFVLWESHAILIYL 72

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 1754571039   1 MQLIGMLDSPYVR--RVAICLKLLGLPYE-HRSLSVFRTfDEFSAINPVVKAPTLVADDGTVLMDSTLILQYLE 71
Cdd:cd03049     1 MKLLYSPTSPYVRkvRVAAHETGLGDDVElVLVNPWSDD-ESLLAVNPLGKIPALVLDDGEALFDSRVICEYLD 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1754571039  14 RVAICLKLLGLPYEHRSLSVFR---TFDEFSAINPVVKAPTLVaDDGTVLMDSTLILQYLE 71
Cdd:cd03042    14 RVRIALNLKGLDYEYVPVNLLKgeqLSPAYRALNPQGLVPTLV-IDGLVLTQSLAIIEYLD 73

GST_N family, Class Tau subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1754571039   1 MQLIGMLDSPYVRRVAICLKLLGLPYEHRSLSVFRTFDEFSAINPVV-KAPTLVADDGTVLmDSTLILQYLE 71
Cdd:cd03058     1 VKLLGAWASPFVLRVRIALALKGVPYEYVEEDLGNKSELLLASNPVHkKIPVLLHNGKPIC-ESLIIVEYID 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1754571039  14 RVAICLKLLGLPYEHRSLSVFRTF---DEFSAINPVVKAPTLVaDDGTVLMDSTLILQYL 70
Cdd:cd03046    13 RILWLLEELGLPYELVLYDRGPGEqapPEYLAINPLGKVPVLV-DGDLVLTESAAIILYL 71

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 1754571039   1 MQLIGMLDSPYVRRVAICLKLLGLPYEHRSLSV---FRTFDEFSAINPVVKAPTLVaDDGTVLMDSTLILQYLES 72
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFgagPEKSPELLKLNPLGKVPALE-DGGKKLTESRAILEYIAR 76

glutathionine S-transferase; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1754571039  38 DEFSAINPVVKAPTLVADDGTVLMDSTLILQYLESLVDAERRLVPMAPEARLRAL 92
Cdd:PRK10542   41 DDYLAINPKGQVPALLLDDGTLLTEGVAIMQYLADSVPDRQLLAPVGSLSRYHTI 95

GST_N family, Metaxin subfamily, Metaxin-like proteins; a heterogenous group of proteins, predominantly uncharacterized, with similarity to metaxins and GSTs. Metaxin 1 is a component of a preprotein import complex of the mitochondrial outer membrane. It extends to the cytosol and is anchored to the mitochondrial membrane through its C-terminal domain. In mice, metaxin is required for embryonic development. In humans, alterations in the metaxin gene may be associated with Gaucher disease. One characterized member of this subgroup is a novel GST from Rhodococcus with toluene o-monooxygenase and gamma-glutamylcysteine synthetase activities. Also members are the cadmium-inducible lysosomal protein CDR-1 and its homologs from C. elegans, and the failed axon connections (fax) protein from Drosophila. CDR-1 is an integral membrane protein that functions to protect against cadmium toxicity and may also have a role in osmoregulation to maintain salt balance in C. elegans. The fax gene of Drosophila was identified as a genetic modifier of Abelson (Abl) tyrosine kinase. The fax protein is localized in cellular membranes and is expressed in embryonic mesoderm and axons of the central nervous system.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1754571039   9 SPYVRRVAICLKLLGLPYEHRSLSVFRTfdefsaiNPVVKAPtLVADDGTVLMDSTLILQYLES 72
Cdd:cd03080    17 SPFCLKVETFLRMAGIPYENKFGGLAKR-------SPKGKLP-FIELNGEKIADSELIIDHLEE 72

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 1754571039   9 SPYVRRVAICLKLLGLPYEHRSLSVF---RTFDEFSAINPVVKAPTLVaDDGTVLMDSTLILQYL 70
Cdd:cd03050     9 SQPSRAVYIFLKLNKIPFEECPIDLRkgeQLTPEFKKINPFGKVPAIV-DGDFTLAESVAILRYL 72