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 2116810011   2 KLYNYFRSSASFRVRIALAIKGLPYEYLPVHLAK-GEHRQAAYGDIAADGLVPLLeLDDGTRLSQSMAIIEYLDDIHPEP 80
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRdGEQRSPEFLALNPQGLVPTL-DIDGEVLTQSLAIIEYLEETYPDP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2116810011  81 ALVPRDALARARVRALAQSIACEIHPINNLRVLKYLSGTLKLDEDAKNTWYRHWVRSGLEAFErQLAQQPASRFCYGDTP 160
Cdd:TIGR01262  80 PLLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEARNRWYQHWISKGFAALE-ALLQPHAGRFCVGDTP 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 2116810011 161 TLADCCLVPQIFNGQRFNTPFDGLPRTMAAFDACMALPAFQQAQPSACPD 210
Cdd:TIGR01262 159 TLADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPD 208

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 2116810011   2 KLYNYFRSSASFRVRIALAIKGLPYEYLPVHLAK-GEHRQAAYGDIAADGLVPLLeLDDGTRLSQSMAIIEYLDDIHPEP 80
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRdGEQRSPEFLALNPQGLVPTL-DIDGEVLTQSLAIIEYLEETYPDP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2116810011  81 ALVPRDALARARVRALAQSIACEIHPINNLRVLKYLSGTLKLDEDAKNTWYRHWVRSGLEAFErQLAQQPASRFCYGDTP 160
Cdd:TIGR01262  80 PLLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEARNRWYQHWISKGFAALE-ALLQPHAGRFCVGDTP 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 2116810011 161 TLADCCLVPQIFNGQRFNTPFDGLPRTMAAFDACMALPAFQQAQPSACPD 210
Cdd:TIGR01262 159 TLADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPD 208

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 2116810011  87 ALARARVRALAQSIACEIHPINNLRVLKYLSGTLKLDEDAKNTWYRHWVRSGLEAFERQLAQQpASRFCYGDTPTLADCC 166
Cdd:cd03191     1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVSEEEKLAWAQHWIERGFQALEKLLAST-AGKYCVGDEPTLADIC 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2116810011 167 LVPQIFNGQRFNTPFDGLPRTMAAFDACMALPAFQQAQPS 206
Cdd:cd03191    80 LVPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPE 119

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2116810011   9 SSASFRVRIALAIKGLPYEYLPVhLAKGEHRQAAYGDIAADGLVPLLELDDGTRLSQSMAIIEYLDDI 76
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELV-DLDPKDKPPELLALNPLGTVPVLVLPDGTVLTDSLVILEYLEEL 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 2116810011   2 KLYNYFRSSASFRVRIALAIKGLPYEYLPVHLAK-GEHRQAAYGDIAADGLVPLLeLDDGTRLSQSMAIIEYLDDIHPEP 80
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRdGEQRSPEFLALNPQGLVPTL-DIDGEVLTQSLAIIEYLEETYPDP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2116810011  81 ALVPRDALARARVRALAQSIACEIHPINNLRVLKYLSGTLKLDEDAKNTWYRHWVRSGLEAFErQLAQQPASRFCYGDTP 160
Cdd:TIGR01262  80 PLLPADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEARNRWYQHWISKGFAALE-ALLQPHAGRFCVGDTP 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 2116810011 161 TLADCCLVPQIFNGQRFNTPFDGLPRTMAAFDACMALPAFQQAQPSACPD 210
Cdd:TIGR01262 159 TLADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPD 208

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 2116810011  87 ALARARVRALAQSIACEIHPINNLRVLKYLSGTLKLDEDAKNTWYRHWVRSGLEAFERQLAQQpASRFCYGDTPTLADCC 166
Cdd:cd03191     1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVSEEEKLAWAQHWIERGFQALEKLLAST-AGKYCVGDEPTLADIC 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2116810011 167 LVPQIFNGQRFNTPFDGLPRTMAAFDACMALPAFQQAQPS 206
Cdd:cd03191    80 LVPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPE 119

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 2116810011   1 MKLYNYFRSSASFRVRIALAIKGLPYEYLPVHLAKGEHRQAAYGDIAADGLVPLLELDDGTRLSQSMAIIEYLD 74
Cdd:cd03051     1 MKLYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAGEQRSPEFLAKNPAGTVPVLELDDGTVITESVAICRYLE 74

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2116810011   1 MKLYnYFRSSASFRVRIALAIKGLPYEYLPVHLAKGEHRQAAYGDIAADGLVPLLELDDGTRLSQSMAIIEYLDDIHP 78
Cdd:cd03057     1 MKLY-YSPGACSLAPHIALEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVLDDGEVLTESAAILQYLADLHP 77

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 2116810011   1 MKLYNYFRSSASFRVRIALAIKGLPYEYLPVHLAKGEHRQAAYGDIAADGLVPLLElDDGTRLSQSMAIIEYL 73
Cdd:cd03056     1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFLALNPNGEVPVLE-LDGRVLAESNAILVYL 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 2116810011   1 MKLYNYFRSSASFRVRIALAIKGLPYEYLPVHLAKGEHRQAAYGDIAADGLVPLLElDDGTRLSQSMAIIEYLDD 75
Cdd:cd03053     2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALE-DGDLKLFESRAITRYLAE 75

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 2116810011   1 MKLYnYFRSSASFRVRIALAIKGLPYEYLPVHLAKGEHRQAAYGDIAADGLVPLLElDDGTRLSQSMAIIEYLDDIHP 78
Cdd:cd03046     1 ITLY-HLPRSRSFRILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLV-DGDLVLTESAAIILYLAEKYG 76

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 2116810011   1 MKLYNYFRSSASFRVRIALAIKGLPYEYLPVHLAKGEHRQAAYGDIAadGLVPLLeLDDGTRLSQSMAIIEYLDDI 76
Cdd:cd03058     1 VKLLGAWASPFVLRVRIALALKGVPYEYVEEDLGNKSELLLASNPVH--KKIPVL-LHNGKPICESLIIVEYIDEA 73

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2116810011   1 MKLYnYFRSSASFRVRIALAIKGLPYEYLPVHLAKGEHRQAA-YGDIAADGLVPLLELDDGTRLSQSMAIIEYLDDIHPE 79
Cdd:PRK10542    1 MKLF-YKPGACSLASHITLRESGLDFTLVSVDLAKKRLENGDdYLAINPKGQVPALLLDDGTLLTEGVAIMQYLADSVPD 79

                          90       100
                  ....*....|....*....|....*..
gi 2116810011  80 PALV-PRDALARARVRALAQSIACEIH 105
Cdd:PRK10542   80 RQLLaPVGSLSRYHTIEWLNYIATELH 106

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2116810011  14 RVRIALAIKGLPYEYLPVHLAKGEHRQAAYGDIAADGLVPLLELDDGTrLSQSMAIIEYLDDIHPE--PALVPRDALARA 91
Cdd:PLN02395   15 RALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYK-IFESRAIMRYYAEKYRSqgPDLLGKTIEERG 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2116810011  92 RVRALAQSIACEIHP-INNLRVLKYLSGTLKLDEDAKNTWYRHWVRSG-LEAFERQLAQqpaSRFCYGDTPTLADCCLVP 169
Cdd:PLN02395   94 QVEQWLDVEATSYHPpLLNLTLHILFASKMGFPADEKVIKESEEKLAKvLDVYEARLSK---SKYLAGDFVSLADLAHLP 170

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 2116810011   2 KLYNYFRSSASFRVRIALAIKGLPYEYLPVHLAKGEHRQAAYGDIAADGLVPLLElDDGTRLSQSMAIIEYL 73
Cdd:cd03050     2 KLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIV-DGDFTLAESVAILRYL 72

GST_N family, Glutaredoxin 2 (GRX2) subfamily; composed of bacterial proteins similar to E. coli GRX2, an atypical GRX with a molecular mass of about 24kD, compared with other GRXs which are 9-12kD in size. GRX2 adopts a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. It contains a redox active CXXC motif located in the N-terminal domain but is not able to reduce ribonucleotide reductase like other GRXs. However, it catalyzes GSH-dependent protein disulfide reduction of other substrates efficiently. GRX2 is thought to function primarily in catalyzing the reversible glutathionylation of proteins in cellular redox regulation including stress responses.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2116810011   1 MKLYNYFRSSASFRVRIALAIKGLPYEYlpVHLAKGEhrQAAYGDIAADGLVPLLELDDGTRLSQSMAIIEYLD 74
Cdd:cd03037     1 MKLYIYEHCPFCVKARMIAGLKNIPVEQ--IILQNDD--EATPIRMIGAKQVPILEKDDGSFMAESLDIVAFID 70

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2116810011  14 RVRIALAIKGLPYEYLPVHLakgEHRQAAYGDIAADGLVPLLELDDGTRLSQSMAIIEYLD 74
Cdd:cd03055    32 RARLVLAAKNIPHEVININL---KDKPDWFLEKNPQGKVPALEIDEGKVVYESLIICEYLD 89

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 2116810011  93 VRALAQSIACEIHPInnLRVLKYLSGTLKLDEDAKNTWYRHWVRSGLEAFERQLAQQPasrFCYGDTPTLADCCLVPQIF 172
Cdd:cd00299     1 VRALEDWADATLAPP--LVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRP---YLAGDQFSLADVALAPVLA 75

                          90
                  ....*....|....
gi 2116810011 173 NGQRFNTPFDGLPR 186
Cdd:cd00299    76 RLEALGPYYDLLDE 89

stringent starvation protein A; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2116810011  12 SFRVRIALAIKGLPYEylpVHLAKGEHRQAAYGDIAADGLVPLLeLDDGTRLSQSMAIIEYLDDIHPEPALVPRDALARA 91
Cdd:PRK09481   22 SHQVRIVLAEKGVSVE---IEQVEKDNLPQDLIDLNPYQSVPTL-VDRELTLYESRIIMEYLDERFPHPPLMPVYPVARG 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2116810011  92 RVRALAQSIAceihpiNNLRVL--KYLSGTLKLDEDAKNTwyrhwVRSGLEAFERQLAQQPasrFCYGDTPTLADCCLVP 169
Cdd:PRK09481   98 ESRLMMHRIE------KDWYSLmnKIVNGSASEADAARKQ-----LREELLAIAPVFGEKP---YFMSEEFSLVDCYLAP 163

GST_N family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi and Alpha. 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. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation and mediation of allergy and inflammation. Other class Sigma members include the class II insect GSTs, S-crystallins from cephalopods and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase and PGD2 synthase activities, and may play an important role in host-parasite interactions. Also members are novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2116810011  15 VRIALAIKGLPYEYlpVHLAKGEHRQAAYGDIAADGLVPLLElDDGTRLSQSMAIIEYL 73
Cdd:cd03039    15 IRLLLADAGVEYED--VRITYEEWPELDLKPTLPFGQLPVLE-IDGKKLTQSNAILRYL 70

GST_N family, Ganglioside-induced differentiation-associated protein 1 (GDAP1) subfamily; GDAP1 was originally identified as a highly expressed gene at the differentiated stage of GD3 synthase-transfected cells. More recently, mutations in GDAP1 have been reported to cause both axonal and demyelinating autosomal-recessive Charcot-Marie-Tooth (CMT) type 4A neuropathy. CMT is characterized by slow and progressive weakness and atrophy of muscles. Sequence analysis of GDAP1 shows similarities and differences with GSTs; it appears to contain both N-terminal TRX-fold and C-terminal alpha helical domains of GSTs, however, it also contains additional C-terminal transmembrane domains unlike GSTs. GDAP1 is mainly expressed in neuronal cells and is localized in the mitochondria through its transmembrane domains. It does not exhibit GST activity using standard substrates.

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gi 2116810011   3 LYNYFRSSASFRVRIALAIKGLPYEYLPVHLAKGEHRQAAYGDIAADGLVPLLeLDDGTRLSQSMAIIEYLD 74
Cdd:cd03052     3 LYHWTQSFSSQKVRLVIAEKGLRCEEYDVSLPLSEHNEPWFMRLNPTGEVPVL-IHGDNIICDPTQIIDYLE 73

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.

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gi 2116810011   3 LYNYFRSSASFRVRIALAIKGLPYEYLPVHLAkgeHRQAAYGDIAADGLVPLLELDDGTRLSQSMAII 70
Cdd:cd03060     3 LYSFRRCPYAMRARMALLLAGITVELREVELK---NKPAEMLAASPKGTVPVLVLGNGTVIEESLDIM 67