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 629721287    5 TLYAYFRSSCSARLRIILNLKNISYDLIPVNLLKD-EQLSAEHKALNPSASVPLLVskrspDAGFKIGQSVAALEYLEEV 83
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRDgEQRSPEFLALNPQGLVPTLD-----IDGEVLTQSLAIIEYLEET 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287   84 HPEVPALPptSDAKGRATVRVLCEIIAADTQPVTNLRIMRRVRALGGSAEE----WNKELMGDGLRAYEAVAKDSAGKYS 159
Cdd:TIGR01262  76 YPDPPLLP--ADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEarnrWYQHWISKGFAALEALLQPHAGRFC 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 629721287  160 VGDNVTMADACLMPALWNAQRFGVDLSQFPTVSRIFANLSEHPAVQKADYFKQPDCP 216
Cdd:TIGR01262 154 VGDTPTLADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 210

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 629721287    5 TLYAYFRSSCSARLRIILNLKNISYDLIPVNLLKD-EQLSAEHKALNPSASVPLLVskrspDAGFKIGQSVAALEYLEEV 83
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRDgEQRSPEFLALNPQGLVPTLD-----IDGEVLTQSLAIIEYLEET 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287   84 HPEVPALPptSDAKGRATVRVLCEIIAADTQPVTNLRIMRRVRALGGSAEE----WNKELMGDGLRAYEAVAKDSAGKYS 159
Cdd:TIGR01262  76 YPDPPLLP--ADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEarnrWYQHWISKGFAALEALLQPHAGRFC 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 629721287  160 VGDNVTMADACLMPALWNAQRFGVDLSQFPTVSRIFANLSEHPAVQKADYFKQPDCP 216
Cdd:TIGR01262 154 VGDTPTLADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 210

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 629721287  96 AKGRATVRVLCEIIAADTQPVTNLRIMRRVRALGGSAEE----WNKELMGDGLRAYEAVAKDSAGKYSVGDNVTMADACL 171
Cdd:cd03191    1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVSEEeklaWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICL 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 629721287 172 MPALWNAQRFGVDLSQFPTVSRIFANLSEHPAVQKA 207
Cdd:cd03191   81 VPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAA 116

stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287  15 SARLRIILNLKNISYDlipVNLLKDEQLSAEHKALNPSASVPLLVskrspDAGFKIGQSVAALEYLEEVHPEVPALPPTS 94
Cdd:PRK09481  22 SHQVRIVLAEKGVSVE---IEQVEKDNLPQDLIDLNPYQSVPTLV-----DRELTLYESRIIMEYLDERFPHPPLMPVYP 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287  95 DAKGRAtvRVLCEIIAADTqpvtnLRIMRRVRAlgGSAEEWN---KELMgDGLRAYEAVAKDSAgkYSVGDNVTMADACL 171
Cdd:PRK09481  94 VARGES--RLMMHRIEKDW-----YSLMNKIVN--GSASEADaarKQLR-EELLAIAPVFGEKP--YFMSEEFSLVDCYL 161

                        170
                 ....*....|....*
gi 629721287 172 MPALWNAQRFGVDLS 186
Cdd:PRK09481 162 APLLWRLPVLGIELS 176

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 629721287    5 TLYAYFRSSCSARLRIILNLKNISYDLIPVNLLKD-EQLSAEHKALNPSASVPLLVskrspDAGFKIGQSVAALEYLEEV 83
Cdd:TIGR01262   1 KLYSYWRSSCSYRVRIALALKGIDYEYVPVNLLRDgEQRSPEFLALNPQGLVPTLD-----IDGEVLTQSLAIIEYLEET 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287   84 HPEVPALPptSDAKGRATVRVLCEIIAADTQPVTNLRIMRRVRALGGSAEE----WNKELMGDGLRAYEAVAKDSAGKYS 159
Cdd:TIGR01262  76 YPDPPLLP--ADPIKRARVRALALLIACDIHPLNNLRVLQYLREKLGVEEEarnrWYQHWISKGFAALEALLQPHAGRFC 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 629721287  160 VGDNVTMADACLMPALWNAQRFGVDLSQFPTVSRIFANLSEHPAVQKADYFKQPDCP 216
Cdd:TIGR01262 154 VGDTPTLADLCLVPQVYNAERFGVDLTPYPTLRRIAAALAALPAFQRAHPENQPDTP 210

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 629721287  96 AKGRATVRVLCEIIAADTQPVTNLRIMRRVRALGGSAEE----WNKELMGDGLRAYEAVAKDSAGKYSVGDNVTMADACL 171
Cdd:cd03191    1 PKKRARVRAIALIIACDIHPLQNLRVLKYLTEKLGVSEEeklaWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICL 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 629721287 172 MPALWNAQRFGVDLSQFPTVSRIFANLSEHPAVQKA 207
Cdd:cd03191   81 VPQVYNARRFGVDLSPYPTIVRINEACLELPAFQAA 116

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 629721287   4 YTLYAYFRSSCSARLRIILNLKNISYDLIPVNLLKDEQLsaEHKALNPSASVPLLVskrspDAGFKIGQSVAALEYLE 81
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQE--EFLALNPLGKVPVLE-----DGGLVLTESLAILEYLA 71

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 629721287   5 TLYAYFRSSCSARLRIILNLKNISYDLIPVNLLKDEQLSAEHKALNPSASVPLLVskrspDAGFKIGQSVAALEYLEE 82
Cdd:cd03053    3 KLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALE-----DGDLKLFESRAITRYLAE 75

GST_N family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p and related GSTs. 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The N-terminal TRX-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. Characterized GSTs in this subfamily include Aspergillus fumigatus GSTs 1 and 2, and Schizosaccharomyces pombe GST-I. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287   3 DYTLYaYFRSSCSARLRIILNLKNISYDLIPVNLLKDEQLSAEHKALNPSASVPLLVSKRSpdAGFKIGQSVAALEYLEE 82
Cdd:cd03048    1 MITLY-THGTPNGFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDHNG--TPLTVFESGAILLYLAE 77

                 ...
gi 629721287  83 VHP 85
Cdd:cd03048   78 KYD 80

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287    2 SDYTLYAYFRSSCSARLRIILNLKNISYDLIPVNLLKDEQLSAEHKALNPSASVPLLVskrspDAGFKIGQSVAALEYLE 81
Cdd:pfam02798   1 MVLTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALE-----DGGKKLTESRAILEYIA 75

                  .
gi 629721287   82 E 82
Cdd:pfam02798  76 R 76

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 629721287   12 SSCSARLRIILNLKNISYDLIPVNLlKDEQLSAEHKALNPSASVPLLVSkrspDAGFKIGQSVAALEYLEE 82
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELVDL-DPKDKPPELLALNPLGTVPVLVL----PDGTVLTDSLVILEYLEE 67

C-terminal, alpha helical domain of Escherichia coli YfcG Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YfcG-like subfamily; composed of the Escherichia coli YfcG 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. YfcG is one of nine GST homologs in Escherichia coli. It is expressed predominantly during the late stationary phase where the predominant form of GSH is glutathionylspermidine (GspSH), suggesting that YfcG might interact with GspSH. It has very low or no GSH transferase or peroxidase activity, but displays a unique disulfide bond reductase activity that is comparable to thioredoxins (TRXs) and glutaredoxins (GRXs). However, unlike TRXs and GRXs, YfcG 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 YcfG reveals a bound GSSG molecule in its active site. The actual physiological substrates for YfcG are yet to be identified.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 629721287 154 SAGKYSVGDNVTMADACLMPALWNAQRFGVDLSQFPTVSRIFANLSEHPAVQKA 207
Cdd:cd10291   57 AKSKYLAGDEYSIADIAIWPWVARHEWQGIDLADFPNLKRWFERLAARPAVQKG 110

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287    6 LYAYFRSSCSARLRIILNLKNISYDLIPVNLlkdEQLSAEHKALNPSASVPLLVskrspDAGFKIGQSVAALEYLEEVHP 85
Cdd:pfam13417   1 LYGFPGSPYARRVRIALNEKGLPYEFVPIPP---GDHPPELLAKNPLGKVPVLE-----DDGGILCESLAIIDYLEELYP 72

                  ...
gi 629721287   86 EVP 88
Cdd:pfam13417  73 GPP 75

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287  13 SCSARLRIILNLKNISYDLIPVNLLKDEQLSAEHKALNPSASVPLLVskrspDAGFKIGQSVAALEYLEEVHPEVPALPP 92
Cdd:PLN02395  11 ASPKRALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIV-----DGDYKIFESRAIMRYYAEKYRSQGPDLL 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287  93 TSDAKGRATVRVLCEIIAADTQP-VTNLRI-MRRVRALGGSAEE----WNKELMGDGLRAYEavAKDSAGKYSVGDNVTM 166
Cdd:PLN02395  86 GKTIEERGQVEQWLDVEATSYHPpLLNLTLhILFASKMGFPADEkvikESEEKLAKVLDVYE--ARLSKSKYLAGDFVSL 163

                 ....*..
gi 629721287 167 ADACLMP 173
Cdd:PLN02395 164 ADLAHLP 170

GST_N family, Beta etherase LigE subfamily; composed of proteins similar to Sphingomonas paucimobilis beta etherase, LigE, a GST-like protein that catalyzes the cleavage of the beta-aryl ether linkages present in low-moleculer weight lignins using GSH as the hydrogen donor. This reaction is an essential step in the degradation of lignin, a complex phenolic polymer that is the most abundant aromatic material in the biosphere. The beta etherase activity of LigE is enantioselective and it complements the activity of the other GST family beta etherase, LigF.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 629721287  17 RLRIILNLKNISYDLIPVNLLKDEQLSAEHKAlNPSASVPLLVSkrspDAGFKIGQSVAALEYLEEVHP 85
Cdd:cd03038   21 KTRLALNHKGLEYKTVPVEFPDIPPILGELTS-GGFYTVPVIVD----GSGEVIGDSFAIAEYLEEAYP 84

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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 629721287 157 KYSVGDNVTMADACLMPALWNAQRFGVDLSQFPTVSRIFANLSEHPAVQKAD 208
Cdd:cd03177   58 DYVAGDQLTIADLSLVATVSTLEVVGFDLSKYPNVAAWYERLKALPPGEEEN 109

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 629721287   5 TLYAYFRSSCSARLRIILNLKNISYDLIPVNLlkdEQLSAEHKALNPSASVPLLVskrspDAGFKIGQSVAALEYLEE 82
Cdd:cd03059    2 TLYSGPDDVYSHRVRIVLAEKGVSVEIIDVDP---DNPPEDLAELNPYGTVPTLV-----DRDLVLYESRIIMEYLDE 71

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287   4 YTLYaYFrsscSAR-----LRIILNLKNISYDLIPVNllKDEQLSAEHKALNPSASVPLLVskrspDAGFKIGQSVAALE 78
Cdd:cd03039    1 YKLT-YF----NIRgrgepIRLLLADAGVEYEDVRIT--YEEWPELDLKPTLPFGQLPVLE-----IDGKKLTQSNAILR 68

                 ..
gi 629721287  79 YL 80
Cdd:cd03039   69 YL 70

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 629721287   3 DYTLYAyfRSSCS--ARLRIILNLKNISYDLIPVNllKDEQLSAEHKALNPSASVPLLV 59
Cdd:cd02976    1 EVTVYT--KPDCPycKATKRFLDERGIPFEEVDVD--EDPEALEELKKLNGYRSVPVVV 55

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 629721287 102 VRVLCEIIAADTQPVTNLRIMRRVRALGGSAE--EWNKELMGDGLRAYEAVAKDsaGKYSVGDNVTMADACLMPALWNAQ 179
Cdd:cd00299    1 VRALEDWADATLAPPLVRLLYLEKVPLPKDEAavEAAREELPALLAALEQLLAG--RPYLAGDQFSLADVALAPVLARLE 78

                         90       100
                 ....*....|....*....|..
gi 629721287 180 RFGV---DLSQFPTVSRIFANL 198
Cdd:cd00299   79 ALGPyydLLDEYPRLKAWYDRL 100