C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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 tumors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197  84 DSEASLIDVMNDGVEDLRLKYIKLIYQEYETGKEAFIKDLPNHLKCFENVLAKN-KTGFLVGDQISFADYNLFDLLLNLK 162
Cdd:cd03210   1 EKEAALIDMVNDGVEDLRLKYVRMIYQNYEAGKDDYIKDLPEQLKPFEKLLAKNnGKGFIVGDKISFADYNLFDLLDIHL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 18858197 163 VLSPSCLDSFPSLKSFVDKISARPKVKALLECENFKKLPINGNGKQ 208
Cdd:cd03210  81 VLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRPINGNGKQ 126

C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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 tumors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197  84 DSEASLIDVMNDGVEDLRLKYIKLIYQEYETGKEAFIKDLPNHLKCFENVLAKN-KTGFLVGDQISFADYNLFDLLLNLK 162
Cdd:cd03210   1 EKEAALIDMVNDGVEDLRLKYVRMIYQNYEAGKDDYIKDLPEQLKPFEKLLAKNnGKGFIVGDKISFADYNLFDLLDIHL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 18858197 163 VLSPSCLDSFPSLKSFVDKISARPKVKALLECENFKKLPINGNGKQ 208
Cdd:cd03210  81 VLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRPINGNGKQ 126

Glutathione S-transferase, C-terminal domain; This domain is closely related to pfam00043.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197    98 EDLRLKYIKLIYQEYETGKEAFIKD-----LPNHLKCFENVLAKNKTGFLVGDQISFADYNLFDLLLNLKV-LSPSCLDS 171
Cdd:pfam14497   1 HDLHHPIASSLYYEDEKKKAKRRKEfreerLPKFLGYFEKVLNKNGGGYLVGDKLTYADLALFQVLDGLLYpKAPDALDK 80

                          90       100
                  ....*....|....*....|..
gi 18858197   172 FPSLKSFVDKISARPKVKALLE 193
Cdd:pfam14497  81 YPKLKALHERVAARPNIKAYLA 102

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197  50 FGQLPKFEDGDLVLFQSNAMLRHLGRKHAA---YGKNDSEA----SLIDVMNDGVE-DLRLKYIKLIYQEYETGKEAFIK 121
Cdd:COG0625  50 LGKVPVLVDDGLVLTESLAILEYLAERYPEpplLPADPAARarvrQWLAWADGDLHpALRNLLERLAPEKDPAAIARARA 129

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18858197 122 DLPNHLKCFENVLAKNktGFLVGDQISFADYNLFDLLLNLKVLSPScLDSFPSLKSFVDKISARPKVKALLE 193
Cdd:COG0625 130 ELARLLAVLEARLAGG--PYLAGDRFSIADIALAPVLRRLDRLGLD-LADYPNLAAWLARLAARPAFQRALA 198

C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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 tumors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197  84 DSEASLIDVMNDGVEDLRLKYIKLIYQEYETGKEAFIKDLPNHLKCFENVLAKN-KTGFLVGDQISFADYNLFDLLLNLK 162
Cdd:cd03210   1 EKEAALIDMVNDGVEDLRLKYVRMIYQNYEAGKDDYIKDLPEQLKPFEKLLAKNnGKGFIVGDKISFADYNLFDLLDIHL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 18858197 163 VLSPSCLDSFPSLKSFVDKISARPKVKALLECENFKKLPINGNGKQ 208
Cdd:cd03210  81 VLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRPINGNGKQ 126

Glutathione S-transferase, C-terminal domain; This domain is closely related to pfam00043.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197    98 EDLRLKYIKLIYQEYETGKEAFIKD-----LPNHLKCFENVLAKNKTGFLVGDQISFADYNLFDLLLNLKV-LSPSCLDS 171
Cdd:pfam14497   1 HDLHHPIASSLYYEDEKKKAKRRKEfreerLPKFLGYFEKVLNKNGGGYLVGDKLTYADLALFQVLDGLLYpKAPDALDK 80

                          90       100
                  ....*....|....*....|..
gi 18858197   172 FPSLKSFVDKISARPKVKALLE 193
Cdd:pfam14497  81 YPKLKALHERVAARPNIKAYLA 102

C-terminal, alpha helical domain of Class Mu Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Mu 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. The class Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1) thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197  86 EASLIDVMNDGVEDLRLKYIKLIYQE-YETGKEAFIKDLPNHLKCFENVLAKNKtgFLVGDQISFADYNLFDLLLNLKVL 164
Cdd:cd03209   2 ERIRVDMLEQQAMDLRMGLIRICYSPdFEKLKPDYLEKLPDKLKLFSEFLGDRP--WFAGDKITYVDFLLYEALDQHRIF 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 18858197 165 SPSCLDSFPSLKSFVDKISARPKVKALLECENFKKLPING 204
Cdd:cd03209  80 EPDCLDAFPNLKDFLERFEALPKISAYMKSDRFIKWPING 119

glutathione s-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197    6 LTYFAVKGRCGALKIMLAD-----KDQQLKENLVTFEEWMKGDLKATCVFGQLPKFEDGDLVLFQSNAMLRHLGRKHAAY 80
Cdd:PTZ00057   7 LYYFDARGKAELIRLIFAYlgieyTDKRFGENGDAFIEFKNFKKEKDTPFEQVPILEMDNIIFAQSQAIVRYLSKKYKIC 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197   81 GKNDSEASLIDVMNDGVEDLRLKYIKL-IYQEYETgkeAFI-KDLPNHLKCFENVLAKNKTGFLVGDQISFADYNLFDLL 158
Cdd:PTZ00057  87 GESELNEFYADMIFCGVQDIHYKFNNTnLFKQNET---TFLnEELPKWSGYFENILKKNHCNYFVGDNLTYADLAVFNLY 163

                        170       180       190
                 ....*....|....*....|....*....|.
gi 18858197  159 LNLKVLSPSCLDSFPSLKSFVDKISARPKVK 189
Cdd:PTZ00057 164 DDIETKYPNSLKNFPLLKAHNEFISNLPNIK 194

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 18858197   4 YTLTYFAVKGRCGALKIMLADKDQQLKENLVTFEEWMKGDLKATCVFGQLPKFEDGDLVLFQSNAMLRHL 73
Cdd:cd00570   1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFLALNPLGKVPVLEDGGLVLTESLAILEYL 70

C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Alpha 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. The class Alpha subfamily is composed of vertebrate GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197  86 EASLIDVMNDGVEDLRLKYIKLIYQEYETGKE--AFIKD--LPNHLKCFENVLAKNKTGFLVGDQISFADYNLFDLLLNL 161
Cdd:cd03208   3 ERALIDMYVEGTADLMEMIMMLPFLPPEEKEAklALIKEkaKNRYFPVFEKVLKDHGQDFLVGNKLSRADVQLLEAILMV 82

                        90       100       110
                ....*....|....*....|....*....|..
gi 18858197 162 KVLSPSCLDSFPSLKSFVDKISARPKVKALLE 193
Cdd:cd03208  83 EELDPSILSDFPLLQAFKTRISNIPTIKKFLQ 114

GST_N family, Class Mu subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1), thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197   5 TLTYFAVKGRCGALKIMLADKDQQLKENLVTF--------EEWMKGDLKATCVFGQLPKFEDGDLVLFQSNAMLRHLGRK 76
Cdd:cd03075   2 TLGYWDIRGLAQPIRLLLEYTGEKYEEKRYELgdapdydrSQWLNEKFKLGLDFPNLPYYIDGDVKLTQSNAILRYIARK 81

                .
gi 18858197  77 H 77
Cdd:cd03075  82 H 82

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197 113 ETGKEAFIKDLPNHLKCFENVLAKNKtgFLVGDQISFADYNLFDLLL---NLKVLspscLDSFPSLKSFVDKISARPKVK 189
Cdd:cd03188  37 EEVKAAARERLERRLAYLDAQLAGGP--YLLGDQFSVADAYLFVVLRwarAVGLD----LSDWPHLAAYLARVAARPAVQ 110

                ...
gi 18858197 190 ALL 192
Cdd:cd03188 111 AAL 113

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18858197 113 ETGKEAFIKDLPNHLKCFENVLAKNktGFLVGDQISFADYNLFDLLLNLKVLSPSC--LDSFPSLKSFVDKI 182
Cdd:cd00299  31 EAAVEAAREELPALLAALEQLLAGR--PYLAGDQFSLADVALAPVLARLEALGPYYdlLDEYPRLKAWYDRL 100

C-terminal, alpha helical domain of Class Omega Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18858197 102 LKYIKLIYQEYETGKEAFIKDLPNhlkcFENVLAKNKTGFLVGDQISFADYNLFD-----LLLNLKVLSPSCLDSFPSLK 176
Cdd:cd03184  20 FYKFLRSGEDRKGLKEELRSALEN----LEEELAKRGTPFFGGNSPGMVDYMIWPwferlEALKLLDGYELCLDRFPKLK 95

                        90       100
                ....*....|....*....|....
gi 18858197 177 SFVDKISARPKVKA-LLECENFKK 199
Cdd:cd03184  96 KWMAAMKQDPAVKAfYTDPETHAE 119

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 18858197 134 LAKNKtgFLVGDQISFADYNLFDLLLNLKVLSPScLDSFPSLKSFVDKISARPKVKA 190
Cdd:cd10291  56 LAKSK--YLAGDEYSIADIAIWPWVARHEWQGID-LADFPNLKRWFERLAARPAVQK 109

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18858197 116 KEAFI-KDLPNHLKCFENVLAKNktGFLVGDQISFADY-NLFDLLLNLKVLSPscLDSFPSLKSFVDKISARP 186
Cdd:cd03189  55 LQAFInPELKRHLDFLEDHLAKH--PYFAGDELTAADImMSFPLEAALARGPL--LEQYPNIAAYLERIEARP 123

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18858197 131 ENVLAKNKtgFLVGDQISFADYNLFDLLLNLKVLSPSCLDSFPSLKSFVDKISARPKVK 189
Cdd:cd03178  53 DKRLSDRP--YLAGEEYSIADIALYPWTHYADLGGFADLSEYPNVKRWLERIAARPAVQ 109

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 18858197 131 ENVLAKNKTGFLVGDQISFAD------YNLFDLLLNLKVLSPSclDSFPSLKSFVDKISARPKVKA 190
Cdd:cd10293  53 ETALAERYRVWLVGDKFTIADlafvpwNNVVDMIFIDPELDIK--KEFPHVYKWLKRMLARPAVKK 116