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 1393428383  94 PKKRASVRMISDLIAGGIQPLQNLSVLKQVG------EEMQLTWAQNAITCGFNALEQILQSTAGIYCVGDEVTMADLCL 167
Cdd:cd03191     1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTeklgvsEEEKLAWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1393428383 168 VPQVANAERFKVDLTPYPTISSINKRLLVLEAFQVSHPCRQ 208
Cdd:cd03191    81 VPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

glutathione transferase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383   9 LYS--YFRSSCSWRVRIALALKGIDYETVPINLikDGGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEEMRPT 86
Cdd:PRK15113    8 LYSdaHFFSPYVMSAFVALQEKGLPFELKTVDL--DAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAP 85

                          90       100       110
                  ....*....|....*....|....*....|
gi 1393428383  87 P---RLLPQDPKKRASVRMI-----SDLIA 108
Cdd:PRK15113   86 PaweRIYPADLQARARARQIqawlrSDLMP 115

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 1393428383  94 PKKRASVRMISDLIAGGIQPLQNLSVLKQVG------EEMQLTWAQNAITCGFNALEQILQSTAGIYCVGDEVTMADLCL 167
Cdd:cd03191     1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTeklgvsEEEKLAWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1393428383 168 VPQVANAERFKVDLTPYPTISSINKRLLVLEAFQVSHPCRQ 208
Cdd:cd03191    81 VPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 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 1393428383   7 PILYSYFRSSCSWRVRIALALKGIDYETVPINLIKdgGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLE 81
Cdd:cd03042     1 MILYSYFRSSASYRVRIALNLKGLDYEYVPVNLLK--GEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYLD 73

glutathione transferase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383   9 LYS--YFRSSCSWRVRIALALKGIDYETVPINLikDGGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEEMRPT 86
Cdd:PRK15113    8 LYSdaHFFSPYVMSAFVALQEKGLPFELKTVDL--DAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAP 85

                          90       100       110
                  ....*....|....*....|....*....|
gi 1393428383  87 P---RLLPQDPKKRASVRMI-----SDLIA 108
Cdd:PRK15113   86 PaweRIYPADLQARARARQIqawlrSDLMP 115

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 1393428383   8 ILYSYFRSSCSWRVRIALALKGIDYETVPINLikDGGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEE 82
Cdd:pfam02798   4 TLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDF--GAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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 1393428383   6 KPILYSYFRSSCSWRVRIALALKGIDYETVPINLIKdgGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEE 82
Cdd:cd03053     1 VLKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTK--GEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAE 75

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383   9 LYSYFRSSCSWRVRIALALKGIDYETVPINLikdggQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEEMRPTPR 88
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPP-----GDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYLEELYPGPP 75

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 1393428383   9 LYsYFRSSCSWRVRIALALKGIDYETVPINLikDGGQQFSKDFQALNPMKQVPTLKI-DGITIHQSLAIIEYLEEMRP 85
Cdd:cd03057     3 LY-YSPGACSLAPHIALEELGLPFELVRVDL--RTKTQKGADYLAINPKGQVPALVLdDGEVLTESAAILQYLADLHP 77

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383  16 SCSWRVRIALALKGIDYETVPINLIKdgGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEEMRPT--PRLLPQD 93
Cdd:PLN02395   11 ASPKRALVTLIEKGVEFETVPVDLMK--GEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYRSqgPDLLGKT 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383  94 PKKRASVRMISDLIAGGIQP-LQNLSVLKQVGEEMQLTWAQNAITCGFNALEQIL-----QSTAGIYCVGDEVTMADLCL 167
Cdd:PLN02395   89 IEERGQVEQWLDVEATSYHPpLLNLTLHILFASKMGFPADEKVIKESEEKLAKVLdvyeaRLSKSKYLAGDFVSLADLAH 168

                  ..
gi 1393428383 168 VP 169
Cdd:PLN02395  169 LP 170

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383  21 VRIALALKGIDYETVPInlikDGGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYL 80
Cdd:cd03039    15 IRLLLADAGVEYEDVRI----TYEEWPELDLKPTLPFGQLPVLEIDGKKLTQSNAILRYL 70

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 1393428383   8 ILYSYFRSSCSWRVRIALALKGIDYETVPINLIKdgGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYL 80
Cdd:cd03050     2 KLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRK--GEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYL 72

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1393428383   9 LYSYFRSSCSWRVRIALALKGIDYETVPINLikdggQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLEE 82
Cdd:cd03059     3 LYSGPDDVYSHRVRIVLAEKGVSVEIIDVDP-----DNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDE 71

putative glutathione S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383  20 RVRIALALKGIDYETV--PINLIKDGGQQFskdfqalNPMKQVPTLKID-GITIHQSLAIIEYLEEMRPTPRLLPQDPKK 96
Cdd:PRK10357   14 KISILLLEKGITFEFVneLPYNADNGVAQY-------NPLGKVPALVTEeGECWFDSPIIAEYIELLNVAPAMLPRDPLA 86

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1393428383  97 RASVRMISDLiAGGIQPLQNLSVLKQV-----GEEMQLTWAQNAITCGFNALEQILQS-TAGiycvGDEVTMADL 165
Cdd:PRK10357   87 ALRVRQLEAL-ADGIMDAALVSVREQArpaaqQSEDELLRQREKINRSLDALEGYLVDgTLK----TDTVNLATI 156

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1393428383 143 LEQILQSTAgiYCVGDEVTMADLCLVPQVANAERFKVDLTPYPTIS 188
Cdd:cd03177    50 LETFLEGSD--YVAGDQLTIADLSLVATVSTLEVVGFDLSKYPNVA 93

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 1393428383  97 RASVRMISDLIAGGIQPLQNLSVLKQVGEEMQLTWAQNAITCGFNALEQILQSTAgiYCVGDEVTMADLCLVPQVANAER 176
Cdd:cd00299     2 RALEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRP--YLAGDQFSLADVALAPVLARLEA 79

                          90       100
                  ....*....|....*....|.
gi 1393428383 177 FKV---DLTPYPTISSINKRL 194
Cdd:cd00299    80 LGPyydLLDEYPRLKAWYDRL 100

GST_N family, Gamma subunit of Elongation Factor 1B (EFB1gamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal TRX-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1393428383   9 LYSYFRSSCSWRVRIALALKGIDYETVPInliKDGGQQFSKDFQALNPMKQVPTLKI-DGITIHQSLAIIEYL 80
Cdd:cd03044     3 LYTYPGNPRSLKILAAAKYNGLDVEIVDF---QPGKENKTPEFLKKFPLGKVPAFEGaDGFCLFESNAIAYYV 72

GSH-dependent disulfide bond oxidoreductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383  20 RVRIALALKGIDYETVPINLIKDGgqQFSKDFQALNPMKQVPTL----KIDG---ITIHQSLAIIEYLEEmrPTPRLLPQ 92
Cdd:PRK13972   14 KITLFLEEAELDYRLIKVDLGKGG--QFRPEFLRISPNNKIPAIvdhsPADGgepLSLFESGAILLYLAE--KTGLFLSH 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383  93 DPKKRASVRMISDLIAGGIQPL--QNLSVLKQVGEEMQLTWAQNAITCG--FNALEQILQSTAgiYCVGDEVTMADLCLV 168
Cdd:PRK13972   90 ETRERAATLQWLFWQVGGLGPMlgQNHHFNHAAPQTIPYAIERYQVETQrlYHVLNKRLENSP--WLGGENYSIADIACW 167

                         170       180
                  ....*....|....*....|....*.
gi 1393428383 169 PQVANAERFKVDLTPYPTISSINKRL 194
Cdd:PRK13972  168 PWVNAWTRQRIDLAMYPAVKNWHERI 193

putative S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383  23 IALALKGIDYETVPINlIKDGgQQFSKDFQALNPMKQVPTLkID-----GITIHQSLAIIEYLEEmrPTPRLLPQDPKKR 97
Cdd:PRK11752   66 LALGVKGAEYDAWLIR-IGEG-DQFSSGFVEINPNSKIPAL-LDrsgnpPIRVFESGAILLYLAE--KFGAFLPKDLAAR 140

                  ...
gi 1393428383  98 ASV 100
Cdd:PRK11752  141 TET 143

NrdH-redoxin (NrdH) family; NrdH is a small monomeric protein with a conserved redox active CXXC motif within a TRX fold, characterized by a glutaredoxin (GRX)-like sequence and TRX-like activity profile. In vitro, it displays protein disulfide reductase activity that is dependent on TRX reductase, not glutathione (GSH). It is part of the NrdHIEF operon, where NrdEF codes for class Ib ribonucleotide reductase (RNR-Ib), an efficient enzyme at low oxygen levels. Under these conditions when GSH is mostly conjugated to spermidine, NrdH can still function and act as a hydrogen donor for RNR-Ib. It has been suggested that the NrdHEF system may be the oldest RNR reducing system, capable of functioning in a microaerophilic environment, where GSH was not yet available. NrdH from Corynebacterium ammoniagenes can form domain-swapped dimers, although it is unknown if this happens in vivo. Domain-swapped dimerization, which results in the blocking of the TRX reductase binding site, could be a mechanism for regulating the oxidation state of the protein.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1393428383   8 ILYSyfRSSCSW--RVRIALALKGIDYETVPInlikDGGQQFSKDFQALNPMKQVPTLKIDG 67
Cdd:cd02976     3 TVYT--KPDCPYckATKRFLDERGIPFEEVDV----DEDPEALEELKKLNGYRSVPVVVIGD 58

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1393428383  12 YFRSSCSW--RVRIALALKGIDYETVPInlikDGGQQFSKDFQALNPMKQVPTLKIDG--ITIHQSLAIIEYLE 81
Cdd:COG0695     5 YTTPGCPYcaRAKRLLDEKGIPYEEIDV----DEDPEAREELRERSGRRTVPVIFIGGehLGGFDEGELDALLA 74

GST_N family, Class Pi 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 Pi GST is a homodimeric eukaryotic protein. The human GSTP1 is mainly found in erythrocytes, kidney, placenta and fetal liver. It is involved in stress responses and in cellular proliferation pathways as an inhibitor of JNK (c-Jun N-terminal kinase). Following oxidative stress, monomeric GSTP1 dissociates from JNK and dimerizes, losing its ability to bind JNK and causing an increase in JNK activity, thereby promoting apoptosis. GSTP1 is expressed in various tumors and is the predominant GST in a wide range of cancer cells. It has been implicated in the development of multidrug-resistant tumours.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1393428383  21 VRIALALKGIDYETVPInlikdGGQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYL 80
Cdd:cd03076    16 IRLLLADQGISWEEERV-----TYEEWQESLKPKMLFGQLPCFKDGDLTLVQSNAILRHL 70

GST_N family, unknown subfamily 2; composed of uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The sequence from Burkholderia cepacia was identified as part of a gene cluster involved in the degradation of 2,4,5-trichlorophenoxyacetic acid. Some GSTs (e.g. Class Zeta and Delta) are known to catalyze dechlorination reactions.

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gi 1393428383  29 GIDYETVPInlikdgGQQFSK----DFQALNPMKQVPTLKIDGITIHQSLAIIEYL 80
Cdd:cd03047    23 GLPYERIDA------GGQFGGldtpEFLAMNPNGRVPVLEDGDFVLWESNAILRYL 72

C-terminal, alpha helical domain of fungal Ure2p Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Ure2p subfamily; composed of the Saccharomyces cerevisiae Ure2p and related fungal proteins. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The N-terminal thioredoxin-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of 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.

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gi 1393428383 143 LEQILQSTAGIYCVGDEVTMADLCLVPQVANAERFKVD-----LTPYPTISSINKRLLVLEAFQ 201
Cdd:cd10293    52 LETALAERYRVWLVGDKFTIADLAFVPWNNVVDMIFIDpeldiKKEFPHVYKWLKRMLARPAVK 115

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 1393428383   8 ILYSYFRSSCSWRVRIALALKGIDYETVPINLIKDggQQFSKDFQALNPMKQVPTLKIDGITIHQSLAIIEYLE 81
Cdd:cd03052     2 VLYHWTQSFSSQKVRLVIAEKGLRCEEYDVSLPLS--EHNEPWFMRLNPTGEVPVLIHGDNIICDPTQIIDYLE 73