C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300073237  89 AFQRAHIRALSLAIACDIHPLNNLRVLKYLKRELGMDDERKNAWIAHWINLGFTALERQLAAdtTRGHFCVGDAPTMADC 168
Cdd:cd03191    1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVSEEEKLAWAQHWIERGFQALEKLLAS--TAGKYCVGDEPTLADI 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 300073237 169 CLVPQIFNARRFEVDMAPYPTLCAIEQACHALPAFQQAHPAQQ 211
Cdd:cd03191   79 CLVPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300073237    4 LYSYFRSSASYRVRIALHLKDLPYETVPVHLlnqggEQLLPAFTEINPHALVPVLAEEGHYVSQSLAMLELLEERHPTPS 83
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPP-----GDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYPGPP 75

C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300073237  89 AFQRAHIRALSLAIACDIHPLNNLRVLKYLKRELGMDDERKNAWIAHWINLGFTALERQLAAdtTRGHFCVGDAPTMADC 168
Cdd:cd03191    1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVSEEEKLAWAQHWIERGFQALEKLLAS--TAGKYCVGDEPTLADI 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 300073237 169 CLVPQIFNARRFEVDMAPYPTLCAIEQACHALPAFQQAHPAQQ 211
Cdd:cd03191   79 CLVPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 300073237   3 TLYSYFRSSASYRVRIALHLKDLPYETVPVHLLNqgGEQLLPAFTEINPHALVPVLAEEGHYVSQSLAMLELLE 76
Cdd:cd03042    2 ILYSYFRSSASYRVRIALNLKGLDYEYVPVNLLK--GEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYLD 73

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 300073237   3 TLYSYFRSSASYRVRIALHLKDLPYETVPVHLLNqgGEQLLPAFTEINPHALVPVLAEEGHYVSQSLAMLELL 75
Cdd:cd03056    2 KLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILK--GETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYL 72

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 300073237   3 TLYSYFRSSASYRVRIALHLKDLPYETVPVHLLnqGGEQLLPAFTEINPHALVPVLAEEGHYVSQSLAMLELLEER 78
Cdd:cd03053    3 KLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLT--KGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 300073237    3 TLYSYFRSSASYRVRIALHLKDLPYETVPVHLLNqgGEQLLPAFTEINPHALVPVLAEEGHYVSQSLAMLELLEE 77
Cdd:pfam02798   4 TLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGA--GPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300073237   10 SSASYRVRIALHLKDLPYETVPVHLLnqgGEQLLPAFTEINPHALVPVLA-EEGHYVSQSLAMLELLEER 78
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELVDLD---PKDKPPELLALNPLGTVPVLVlPDGTVLTDSLVILEYLEEL 68

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 300073237   3 TLYsYFRSSASYRVRIALHLKDLPYETVPVHLlnQGGEQLLPAFTEINPHALVPVLAEEGHYVSQSLAMLELLEERHP 80
Cdd:cd03046    2 TLY-HLPRSRSFRILWLLEELGLPYELVLYDR--GPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 76

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300073237   2 TTLYsYFRSSASYRVRIALHLKDLPYETVPVHLLnqGGEQLLPAFTEINPHALVPVLA-EEGHYVSQSLAMLELLEERHP 80
Cdd:cd03057    1 MKLY-YSPGACSLAPHIALEELGLPFELVRVDLR--TKTQKGADYLAINPKGQVPALVlDDGEVLTESAAILQYLADLHP 77

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300073237  13 SYRVRIALHLKDLPYETVPVHLLNQggeqllPA-FTEINPHALVPVLAEEGHYVSQSLAMLELLEERHPTPSL 84
Cdd:PLN02817  76 CQRVLLTLEEKHLPYDMKLVDLTNK------PEwFLKISPEGKVPVVKLDEKWVADSDVITQALEEKYPDPPL 142

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 300073237   4 LYSYFRSSASYRVRIALHLKDLPYETVPVHLLNqgGEQLLPAFTEINPHALVPVLAEEGHYVSQSLAMLELLEERH 79
Cdd:cd03050    3 LYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRK--GEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

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 300073237  90 FQRAH-IRALSLaIACDIHPlnNLRVLKYLKRELGMDD-ERKNAWIAHWINLGFTALERQLAAdttrGHFCVGDAPTMAD 167
Cdd:cd03188    1 LERARlLEWLNF-IASELHK--AFGPLFYPARWADDALaEEVKAAARERLERRLAYLDAQLAG----GPYLLGDQFSVAD 73

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 300073237 168 CCLVPQIFNARRFEVDMAPYPTLCAIEQACHALPAFQQAH 207
Cdd:cd03188   74 AYLFVVLRWARAVGLDLSDWPHLAAYLARVAARPAVQAAL 113

glutathione S-transferase

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 300073237  11 SASYRVRIALHLKDLPYETVPVHLLNqgGEQLLPAFTEINPHALVPVLAEEGHYVSQSLAMLELLEERHPT--PSLL 85
Cdd:PLN02395  11 ASPKRALVTLIEKGVEFETVPVDLMK--GEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYRSqgPDLL 85

C-terminal, alpha helical domain of an unknown subfamily 7 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 7; 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 300073237 141 FTALERQLAadttrGH-FCVGDAPTMADCCLVPQIFNARRFEVDMAPYPTLCAIEQACHALPAF 203
Cdd:cd03206   42 LRLLDQHLA-----GRdWLAGDRPTIADVACYPYIALAPEGGVSLEPYPAIRAWLARVEALPGF 100

GST_N family, Omega-like subfamily; composed of uncharacterized proteins with similarity to class Omega 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. 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. Like Omega enzymes, proteins in this subfamily 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 300073237   4 LYSYFRSSASYRVRIALHLKDLPYETVPVHLLNQGgeqllPAFTEINPHALVPVLA-EEGHYVSQSL 69
Cdd:cd03060    3 LYSFRRCPYAMRARMALLLAGITVELREVELKNKP-----AEMLAASPKGTVPVLVlGNGTVIEESL 64