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 490929770 140 FILAELKTQLFFQGLGRMKAENVEEEFRRHLDRIEQVLSQSEWLVGDSQTIADIAVVAQLgEVVRTSKKFSKEILDRPFI 219
Cdd:cd00299   15 PLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVL-ARLEALGPYYDLLDEYPRL 93

                 ....*.
gi 490929770 220 ALWYKK 225
Cdd:cd00299   94 KAWYDR 99

Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490929770   13 PFCQKVSRILKFKGISFETVNYNGilgakvPLLSKVGKVPVIDHNGQRIQDSTRIARYLEEAYPD-TPRLYPEdpnQKAL 91
Cdd:pfam17172   1 PFCLKVETYLRMAGIPYEVEPSSN------PSASPKGKLPFIELNGDLIADSEFIIEFLKEKGVDlDAGLSPE---QKAD 71

                          90       100
                  ....*....|....*....|....*
gi 490929770   92 AELWEDWADEALYFYEVYLRVNDPE 116
Cdd:pfam17172  72 ARALKALVEEHLYWALLYERWLDPE 96

putative glutathione S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490929770  12 SPFCQKVSRILKFKGISFETVN---YNGilGAKVPLLSKVGKVPV-IDHNGQRIQDSTRIARYLEEAYPdTPRLYPEDPn 87
Cdd:PRK10357   9 SPFVRKISILLLEKGITFEFVNelpYNA--DNGVAQYNPLGKVPAlVTEEGECWFDSPIIAEYIELLNV-APAMLPRDP- 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490929770  88 qkalaelwedwadealyfyEVYLRVNDPEALKEAIRISSI------GRPAYERPmvkgfilaelKTQLFFQglgrmkaen 161
Cdd:PRK10357  85 -------------------LAALRVRQLEALADGIMDAALvsvreqARPAAQQS----------EDELLRQ--------- 126

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 490929770 162 vEEEFRRHLDRIEQVLSQSEwLVGDSQTIADIAVVAQLG 200
Cdd:PRK10357 127 -REKINRSLDALEGYLVDGT-LKTDTVNLATIAIACAVG 163

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 490929770 140 FILAELKTQLFFQGLGRMKAENVEEEFRRHLDRIEQVLSQSEWLVGDSQTIADIAVVAQLgEVVRTSKKFSKEILDRPFI 219
Cdd:cd00299   15 PLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVL-ARLEALGPYYDLLDEYPRL 93

                 ....*.
gi 490929770 220 ALWYKK 225
Cdd:cd00299   94 KAWYDR 99

Glutathione S-transferase N-terminal domain; This domain is homologous to pfam02798.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490929770   13 PFCQKVSRILKFKGISFETVNYNGilgakvPLLSKVGKVPVIDHNGQRIQDSTRIARYLEEAYPD-TPRLYPEdpnQKAL 91
Cdd:pfam17172   1 PFCLKVETYLRMAGIPYEVEPSSN------PSASPKGKLPFIELNGDLIADSEFIIEFLKEKGVDlDAGLSPE---QKAD 71

                          90       100
                  ....*....|....*....|....*
gi 490929770   92 AELWEDWADEALYFYEVYLRVNDPE 116
Cdd:pfam17172  72 ARALKALVEEHLYWALLYERWLDPE 96

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 490929770   4 IILHQWEISPFCQKVSRILKFKGISFETVNYNGILGAKVPLLSK--VGKVPVIDHNGQRIQDSTRIARYLE 72
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFLALnpLGKVPVLEDGGLVLTESLAILEYLA 71

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 490929770   12 SPFCQKVSRILKFKGISFETVNYNGILGAKVPLLSKV---GKVPVI-DHNGQRIQDSTRIARYLEEA 74
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 490929770   20 RI-LKFKGISFETVNYNGI-----LGAKVPLLSKVGKVPVIDHNGQRIQDSTRIARYLEEAYPDtPRLYPEDPNQKALAe 93
Cdd:TIGR01262  15 RIaLALKGIDYEYVPVNLLrdgeqRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETYPD-PPLLPADPIKRARV- 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490929770   94 lwedwadealyfyevylrvndpEALKEAIRiSSIgrpayeRPMVKGFILAELktqlffqglgrMKAENVEEEFRRH---- 169
Cdd:TIGR01262  93 ----------------------RALALLIA-CDI------HPLNNLRVLQYL-----------REKLGVEEEARNRwyqh 132

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 490929770  170 -----LDRIEQVLSQS--EWLVGDSQTIADIAVVAQL 199
Cdd:TIGR01262 133 wiskgFAALEALLQPHagRFCVGDTPTLADLCLVPQV 169

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 490929770 140 FILAELKTQLFFQGLGRMKAENVEEEFRRHLDRIEQVLSQSEWLVGDSQTIADIAVVAQLgEVVRTSKKFSKEILDRPFI 219
Cdd:cd00299   15 PLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVL-ARLEALGPYYDLLDEYPRL 93

                 ....*.
gi 490929770 220 ALWYKK 225
Cdd:cd00299   94 KAWYDR 99

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490929770  12 SPFCQKVSRILKFKGISFE--TVNyngiLGAKVPL------LSKVGKVPVIDHNGQRIQDSTRIARYLEEAYPDT--PRL 81
Cdd:PRK15113  16 SPYVMSAFVALQEKGLPFElkTVD----LDAGEHLqptyqgYSLTRRVPTLQHDDFELSESSAIAEYLEERFAPPawERI 91

                         90
                 ....*....|.
gi 490929770  82 YPEDPNQKALA 92
Cdd:PRK15113  92 YPADLQARARA 102

C-terminal, alpha helical domain of GTT1-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490929770 135 PMVKGFILAELK--TQLFFQGLGRMKAENVEE-----EFRRHLDRIEQVLSQSEWLVGDSQTIADIavvaQLGEVVRTSK 207
Cdd:cd03189   25 PLLLKLVFGKIGeaPPPFFRPISRKIADKPLQafinpELKRHLDFLEDHLAKHPYFAGDELTAADI----MMSFPLEAAL 100

                         90
                 ....*....|....*
gi 490929770 208 KFSKEILDRPFIALW 222
Cdd:cd03189  101 ARGPLLEQYPNIAAY 115

C-terminal, alpha helical domain of Escherichia coli Yghu Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YghU-like subfamily; composed of the Escherichia coli YghU and related proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YghU is one of nine GST homologs in the genome of Escherichia coli. It is similar to Escherichia coli YfcG in that it has poor GSH transferase activity towards typical substrates. It shows modest reductase activity towards some organic hydroperoxides. Like YfcG, YghU also shows good disulfide bond oxidoreductase activity comparable to the activities of glutaredoxins and thioredoxins. YghU does not contain a redox active cysteine residue, and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YghU reveals two GSH molecules bound in its active site.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 490929770 165 EFRRHLDRIEQVLSQSEWLVGDSQTIADIAVVAQLGEVVRTSKKFSKEILD 215
Cdd:cd10292   44 EAKRQLDVLDRQLATHKYLAGDEYTIADMAIWPWYGGLALGSLYDAAEFLD 94

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
                 ....*....|....*....|....*....|....*..
gi 490929770 159 AENVEEEFRRHLDRIEQVLSQSEWLVGDSQTIADIAV 195
Cdd:cd03206   31 PERARAISHRLLRLLDQHLAGRDWLAGDRPTIADVAC 67

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 490929770  13 PFCQKVSRILKFKGISFETVNYNGILGAKVPLLSKVGK--VPVIDHNGQRI--QDSTRIARYLE 72
Cdd:COG0695   11 PYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRrtVPVIFIGGEHLggFDEGELDALLA 74

C-terminal, alpha helical domain of an unknown subfamily 5 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 5; 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
                 ....*....|....*....|....*....|....*....|
gi 490929770 160 ENVEEEFR----RHLDRIEQVLSQSEWLVGDSQTIADIAV 195
Cdd:cd03196   36 EDDEEEYRaqaeEFLAELEARLSQHAYLFGDRPSLADYAI 75

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 490929770   4 IILHQWEISPFCQKVSRILKFKGISFETVNYNGILGA-KVPLLSKV---GKVPVIDHNGQRIQDSTRIARYL 71
Cdd:cd03056    1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKGEtRTPEFLALnpnGEVPVLELDGRVLAESNAILVYL 72

C-terminal, alpha helical domain of Class Sigma-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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-like members include the class II insect GSTs, S-crystallins from cephalopods, nematode-specific GSTs, 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. Members also include 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
                 ....*....|....*....|....*....|....*....|....
gi 490929770 156 RMKAENVEEEFRRHLDRIEQVLSQS--EWLVGDSQTIADIAVVA 197
Cdd:cd03192   34 EKKKEFLEEALPKFLGKFEKILKKSggGYFVGDKLTWADLALFD 77

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490929770  25 KGISFETVNYNGILGA-KVP---LLSKVGKVPVIDHNGQRIQDSTRIARYLEEAYPDT-PRLYPEDPNQKALAELWedwa 99
Cdd:PLN02395  23 KGVEFETVPVDLMKGEhKQPeylALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYRSQgPDLLGKTIEERGQVEQW---- 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490929770 100 dealyfYEVYLRVNDPEALKEAIRI---SSIGRPAYERPMvkgfilaelktqlffqglgrmkaENVEEEFRRHLDRIEQV 176
Cdd:PLN02395  99 ------LDVEATSYHPPLLNLTLHIlfaSKMGFPADEKVI-----------------------KESEEKLAKVLDVYEAR 149

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 490929770 177 LSQSEWLVGDSQTIADIAVVAQLGEVVRTSKKfSKEILDRPFIALWYKK 225
Cdd:PLN02395 150 LSKSKYLAGDFVSLADLAHLPFTEYLVGPIGK-AYLIKDRKHVSAWWDD 197

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 490929770  159 AENVEEEFRRHLDRIEQVLSQSEWLVGDSQTIADIAVVAQLGEVVRTSKKFSKEilDRPFIALWYK 224
Cdd:pfam00043  24 VDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIALAPALLWLYELDPACLRE--KFPNLKAWFE 87

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 490929770 152 QGLGRMKAeNVEEEFRRHLDRIEQVLSQSEWLVGDSQTIADiavvAQLGEVVRTSKKFSKEILDRPFIALWYKK 225
Cdd:cd03188   34 ALAEEVKA-AARERLERRLAYLDAQLAGGPYLLGDQFSVAD----AYLFVVLRWARAVGLDLSDWPHLAAYLAR 102

putative S-transferase; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 490929770 165 EFRRHLDRIEQVLSQSEWLVGDSQTIADIAVVAQLGEVVR 204
Cdd:PRK11752 182 EAKRQLDVLDKQLAEHEYIAGDEYTIADIAIWPWYGNLVL 221

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 490929770  13 PFCQKVSRILKFKGISFETVNYNgiLGAKvP--LLSK--VGKVPVIDHN-GQRIQDSTRIARYLE 72
Cdd:cd03055   28 PYAQRARLVLAAKNIPHEVININ--LKDK-PdwFLEKnpQGKVPALEIDeGKVVYESLIICEYLD 89

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.

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gi 490929770 170 LDRIEQVLSQSEWLVGDSQTIADIAVVA 197
Cdd:cd03177   47 LEFLETFLEGSDYVAGDQLTIADLSLVA 74

C-terminal, alpha helical domain of Metaxin and related proteins; Glutathione S-transferase (GST) C-terminal domain family, Metaxin subfamily; composed of metaxins and related proteins. 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. Metaxin 2 binds to metaxin 1 and may also play a role in protein translocation into the mitochondria. Genome sequencing shows that a third metaxin gene also exists in zebrafish, Xenopus, chicken, and mammals. Sequence analysis suggests that all three metaxins share a common ancestry and that they possess similarity to GSTs. Also included in the subfamily are uncharacterized proteins with similarity to metaxins, including a novel GST from Rhodococcus with toluene o-monooxygenase and glutamylcysteine synthetase activities. Other 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.

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gi 490929770 143 AELKTQLFFQGLGRmkaenVEEEFRRHLDRIEQVLSQSEWLVGDSQTIADIAVVAQLGEVVRTS 206
Cdd:cd03193    6 RMVETHLYWALRRE-----IYELALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLASILYPP 64

Glutaredoxin;

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gi 490929770   13 PFCQKVSRILKFKGISFETVNY--NGILGAKVPLLSKVGKVPVIDHNGQRI 61
Cdd:pfam00462  10 PFCKRAKRLLKSLGVDFEEIDVdeDPEIREELKELSGWPTVPQVFIDGEHI 60