Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760   1 MLRILGKASSINVRKVLWACEELNISFSREEWGSGFKSTDTEEFLTLNPNAMVPVIIDDGFVLWESNSILRYLAARYNGC 80
Cdd:COG0625     1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760  81 HLYPLEPIARARIDQWIDWQSADLNPAWGYAFMSLvrRSADHQDVVATAAscANWVRYMQILDQQLEmTGAYVSGETFTL 160
Cdd:COG0625    81 PLLPADPAARARVRQWLAWADGDLHPALRNLLERL--APEKDPAAIARAR--AELARLLAVLEARLA-GGPYLAGDRFSI 155

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1500006760 161 ADIPVGLSVNRWFETPLDHPDLPAVNMYYERLSSRPGY 198
Cdd:COG0625   156 ADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAF 193

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760   1 MLRILGKASSINVRKVLWACEELNISFSREEWGSGFKSTDTEEFLTLNPNAMVPVIIDDGFVLWESNSILRYLAARYNGC 80
Cdd:COG0625     1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760  81 HLYPLEPIARARIDQWIDWQSADLNPAWGYAFMSLvrRSADHQDVVATAAscANWVRYMQILDQQLEmTGAYVSGETFTL 160
Cdd:COG0625    81 PLLPADPAARARVRQWLAWADGDLHPALRNLLERL--APEKDPAAIARAR--AELARLLAVLEARLA-GGPYLAGDRFSI 155

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1500006760 161 ADIPVGLSVNRWFETPLDHPDLPAVNMYYERLSSRPGY 198
Cdd:COG0625   156 ADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAF 193

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 1500006760   2 LRILGKASSINVRKVLWACEELNISFSREEWGSGFKSTDTEEFLTLNPNAMVPVIIDDGFVLWESNSILRYLA 74
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIA 75

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760   1 MLRILGKASSINVRKVLWACEELNISFSREEWGSGFKSTDTEEFLTLNPNAMVPVIIDDGFVLWESNSILRYLAARYNGC 80
Cdd:COG0625     1 MMKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760  81 HLYPLEPIARARIDQWIDWQSADLNPAWGYAFMSLvrRSADHQDVVATAAscANWVRYMQILDQQLEmTGAYVSGETFTL 160
Cdd:COG0625    81 PLLPADPAARARVRQWLAWADGDLHPALRNLLERL--APEKDPAAIARAR--AELARLLAVLEARLA-GGPYLAGDRFSI 155

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1500006760 161 ADIPVGLSVNRWFETPLDHPDLPAVNMYYERLSSRPGY 198
Cdd:COG0625   156 ADIALAPVLRRLDRLGLDLADYPNLAAWLARLAARPAF 193

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1500006760   2 LRILGKASSINVRKVLWACEELNISFSREEWGSGFKSTDTEEFLTLNPNAMVPVIIDDGFVLWESNSILRYLA 74
Cdd:cd03047     1 LTIWGRRSSINVQKVLWLLDELGLPYERIDAGGQFGGLDTPEFLAMNPNGRVPVLEDGDFVLWESNAILRYLA 73

GST_N family, Saccharomyces cerevisiae GTT1-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT1, and the Schizosaccharomyces pombe GST-III. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GTT1, a homodimer, exhibits GST activity with standard substrates and associates with the endoplasmic reticulum. Its expression is induced after diauxic shift and remains high throughout the stationary phase. S. pombe GST-III is implicated in the detoxification of various metals.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1500006760  16 VLWACEELNISFSREEWGSGFKSTDTEEFLTLNPNAMVPVIIDDGFVLWESNSILRYLAARY 77
Cdd:cd03046    14 ILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKY 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760  12 NVRKVLWACEELNISFSREEWGSGFKSTDTEEFLTLNPNAMVPVIID---DGFVLWESNSILRYLAARYN 78
Cdd:cd03048    11 NGFKVSIMLEELGLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDhngTPLTVFESGAILLYLAEKYD 80

GSH-dependent disulfide bond oxidoreductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760  43 EFLTLNPNAMVPVIID----DG---FVLWESNSILRYLAARyNGCHLyPLEPIARARIDQWIDWQSADLNPAWGYAFMsl 115
Cdd:PRK13972   42 EFLRISPNNKIPAIVDhspaDGgepLSLFESGAILLYLAEK-TGLFL-SHETRERAATLQWLFWQVGGLGPMLGQNHH-- 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760 116 VRRSADHQDVVATAASCANWVRYMQILDQQLEmTGAYVSGETFTLADIPVGLSVNRWFETPLDHPDLPAVNMYYERLSSR 195
Cdd:PRK13972  118 FNHAAPQTIPYAIERYQVETQRLYHVLNKRLE-NSPWLGGENYSIADIACWPWVNAWTRQRIDLAMYPAVKNWHERIRSR 196

                  ..
gi 1500006760 196 PG 197
Cdd:PRK13972  197 PA 198

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 1500006760   2 LRILGKASSINVRKVLWACEELNISFSRE--EWGSGFKSTdtEEFLTLNPNAMVPVIIDDGFVLWESNSILRYLAAR 76
Cdd:cd03053     2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVpvDLTKGEHKS--PEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1500006760  14 RKVLWACEELNISFSREEWGSGFKSTDTEEFLTLNPNAMVPVIIDDGFVLWESNSILRYLAARY 77
Cdd:cd03050    13 RAVYIFLKLNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

Glutathione S-transferase C-terminal-like, alpha helical domain of the Gamma subunit of Elongation Factor 1B and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Gamma subunit of Elongation Factor 1B (EF1Bgamma) 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 thioredoxin-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 to 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. Also included in this subfamily is the GST_C-like domain at the N-terminus of human valyl-tRNA synthetase (ValRS) and its homologs. Metazoan ValRS forms a stable complex with Elongation Factor-1H (EF-1H), and together, they catalyze consecutive steps in protein biosynthesis, tRNA aminoacylation and its transfer to EF.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760  89 ARARIDQWIDWQSADLNPAWGYAFMSLVRRSADHQDVVATAASCANWVryMQILDQQLEmTGAYVSGETFTLADIPVGLS 168
Cdd:cd03181     1 EAAQVLQWISFANSELLPAAATWVLPLLGIAPYNKKAVDKAKEDLKRA--LGVLEEHLL-TRTYLVGERITLADIFVASA 77

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1500006760 169 VNRWFETPLDHPDL---PAVNMYYERLSSRPGY 198
Cdd:cd03181    78 LLRGFETVLDPEFRkkyPNVTRWFNTVVNQPKF 110

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760  43 EFLTLNPNAMVPVIIDDGFVLWESNSILRYLAARY--NGCHLYPLEPIARARIDQWIDWQSADLNPA-----WGYAFMSL 115
Cdd:PLN02395   43 EYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYrsQGPDLLGKTIEERGQVEQWLDVEATSYHPPllnltLHILFASK 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760 116 VRRSADHQDVVATAASCAnwvRYMQILDQQLEMTgAYVSGETFTLADIPvGLSVNRWFETPLDH----PDLPAVNMYYER 191
Cdd:PLN02395  123 MGFPADEKVIKESEEKLA---KVLDVYEARLSKS-KYLAGDFVSLADLA-HLPFTEYLVGPIGKayliKDRKHVSAWWDD 197

                  ....*..
gi 1500006760 192 LSSRPGY 198
Cdd:PLN02395  198 ISSRPAW 204

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1500006760  18 WACEELNISFSREEWGSGFKSTDTEEFLTLNPNAMVPV-IIDDGFVLWESNSILRYLAARY 77
Cdd:cd03057    16 IALEELGLPFELVRVDLRTKTQKGADYLAINPKGQVPAlVLDDGEVLTESAAILQYLADLH 76

GST_N family, unknown subfamily 1; composed of uncharacterized proteins, predominantly from bacteria, 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1500006760  18 W-ACEELNISFsREEWGSGFKSTDTEEFLTLNPNAMVPVIIDDGFVLWESNSILRYLA 74
Cdd:cd03043    17 WlLLKAAGIPF-EEILVPLYTPDTRARILEFSPTGKVPVLVDGGIVVWDSLAICEYLA 73

glutathione transferase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1500006760  53 VPVIIDDGFVLWESNSILRYLAARYNGCH---LYPLEPIARARIDQWIDWQSADLNP 106
Cdd:PRK15113   59 VPTLQHDDFELSESSAIAEYLEERFAPPAwerIYPADLQARARARQIQAWLRSDLMP 115

putative S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760  30 EEWGSGFkstdteefLTLNPNAMVPVIIDDG----FVLWESNSILRYLAARYNgcHLYPLEPIARARIDQWIDWQ--SAd 103
Cdd:PRK11752   86 DQFSSGF--------VEINPNSKIPALLDRSgnppIRVFESGAILLYLAEKFG--AFLPKDLAARTETLNWLFWQqgSA- 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760 104 lnPAWG--------YA----------FMSLVRRSADhqdvvataascanwvrymqILDQQLEmTGAYVSGETFTLADIPV 165
Cdd:PRK11752  155 --PFLGggfghfyaYApekieyainrFTMEAKRQLD-------------------VLDKQLA-EHEYIAGDEYTIADIAI 212

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
                  ....*....|....*....|....*....|....*....|
gi 1500006760  36 FKSTDTEEFLTLNPNAMVPVII-DDGFVLWESNSILRYLA 74
Cdd:cd03044    34 GKENKTPEFLKKFPLGKVPAFEgADGFCLFESNAIAYYVA 73

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1500006760  90 RARIDQWIDWQSADLNPAWGYA--FmslvRRSADHQdvVATAAScanwvRYMQ-------ILDQQLEMTGaYVSGETFTL 160
Cdd:cd10291     2 RYAVLQWLMWQMGGLGPMQGQAhhF----KRYAPEK--IPYAIK-----RYTNetkrlygVLDRRLAKSK-YLAGDEYSI 69

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1500006760 161 ADIPVGLSVNRWFETPLDHPDLPAVNMYYERLSSRPG 197
Cdd:cd10291    70 ADIAIWPWVARHEWQGIDLADFPNLKRWFERLAARPA 106

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 1500006760  93 IDQWIDWQSADLNPAWGYAFMSLVRRSADHQDVVATAAscANWVRYMQILDQQLEmTGAYVSGETFTLADIPVGlSVNRW 172
Cdd:cd00299     1 VRALEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAR--EELPALLAALEQLLA-GRPYLAGDQFSLADVALA-PVLAR 76

                          90       100
                  ....*....|....*....|....
gi 1500006760 173 FETPLDHPDL----PAVNMYYERL 192
Cdd:cd00299    77 LEALGPYYDLldeyPRLKAWYDRL 100

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 1500006760  18 WACEELNISF-----SREEWGS-GFKSTdteefltlNPNAMVPVIIDDGFVLWESNSILRYLA 74
Cdd:cd03039    17 LLLADAGVEYedvriTYEEWPElDLKPT--------LPFGQLPVLEIDGKKLTQSNAILRYLA 71

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.

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gi 1500006760  25 ISFSREEWGSGFKSTdteefltlNPNAMVPVIIDDGFVLWESNSILRYLA 74
Cdd:cd03076    30 ERVTYEEWQESLKPK--------MLFGQLPCFKDGDLTLVQSNAILRHLG 71

C-terminal, alpha helical domain of Ure2p and related Glutathione S-transferase-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p, YfcG and YghU from Escherichia coli, and related GST-like 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. YfcG and YghU are two of the nine GST homologs in the genome of Escherichia coli. They display very low or no GSH transferase, but show very good disulfide bond oxidoreductase activity. YghU also shows modest organic hydroperoxide reductase 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 1500006760  89 ARARIDQWIDWQSADLNPA-----WGYAFMSLVRRSA--DHQDVVAtaascanwvRYMQILDQQLEMTGaYVSGETFTLA 161
Cdd:cd03178     1 ERAEVLQWLFFQMSGLGPMfgqagHFLYFAPEKIPYAieRYTDEVK---------RLYGVLDKRLSDRP-YLAGEEYSIA 70

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gi 1500006760 162 DI---PVGLSVNRWFETPLDhpDLPAVNMYYERLSSRPG 197
Cdd:cd03178    71 DIalyPWTHYADLGGFADLS--EYPNVKRWLERIAARPA 107