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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 139 GRAEALNWLFWLQGSAPYLGGGFGHFYHYAPQKIEYAINRFTMEAKRQLDVLDRQLAQHRFIAGDAYSIADIAIWPWYGN 218
Cdd:cd10292     1 KRTETLNWLFWQMGSAPYLGGGFGHFYSYAPVKIEYAIDRFTMEAKRQLDVLDRQLATHKYLAGDEYTIADMAIWPWYGG 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1755442227 219 LIIGGLYEASKFLQVDEYKNVKRWAEEVAQRPAVQRGR 256
Cdd:cd10292    81 LALGSLYDAAEFLDVDEYKHVQRWAKDIAARPAVKRGR 118

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 1755442227  44 PLQLYS-LGTPNGQKVTILLEELlalgisGAEYDAHLIRISEGDQFSSGFVEVNPNSKIPALLDRSVTpavrVFESGAIL 122
Cdd:pfam02798   2 VLTLYGiRGSPRAHRIRWLLAEK------GVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKK----LTESRAIL 71

                  ....*
gi 1755442227 123 LYLAD 127
Cdd:pfam02798  72 EYIAR 76

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 139 GRAEALNWLFWLQGSAPYLGGGFGHFYHYAPQKIEYAINRFTMEAKRQLDVLDRQLAQHRFIAGDAYSIADIAIWPWYGN 218
Cdd:cd10292     1 KRTETLNWLFWQMGSAPYLGGGFGHFYSYAPVKIEYAIDRFTMEAKRQLDVLDRQLATHKYLAGDEYTIADMAIWPWYGG 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1755442227 219 LIIGGLYEASKFLQVDEYKNVKRWAEEVAQRPAVQRGR 256
Cdd:cd10292    81 LALGSLYDAAEFLDVDEYKHVQRWAKDIAARPAVKRGR 118

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 140 RAEALNWLFWLQGSAPYLGGGFGHFYHYAPQKIEYAINRFTMEAKRQLDVLDRQLAQHRFIAGDAYSIADIAIWPWYGNL 219
Cdd:cd03178     2 RAEVLQWLFFQMSGLGPMFGQAGHFLYFAPEKIPYAIERYTDEVKRLYGVLDKRLSDRPYLAGEEYSIADIALYPWTHYA 81

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1755442227 220 IIGGlyeaskFLQVDEYKNVKRWAEEVAQRPAVQR 254
Cdd:cd03178    82 DLGG------FADLSEYPNVKRWLERIAARPAVQK 110

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 1755442227  44 PLQLYSLGTPNGQKVTILLEELlalgisGAEYDAHLIRISEGDQFSSGFVEVNPNSKIPALLDRSVTPaVRVFESGAILL 123
Cdd:cd03048     1 MITLYTHGTPNGFKVSIMLEEL------GLPYEIHPVDISKGEQKKPEFLKINPNGRIPAIVDHNGTP-LTVFESGAILL 73

                  ....*...
gi 1755442227 124 YLADKFGQ 131
Cdd:cd03048    74 YLAEKYDK 81

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 141 AEALNWLFW-LQGSAPYLGGgFGHFYHYAPQKIEYAINRFTMEAKRQLDVLDRQLAQH--RFIAGDAYSIADIAIWPWyg 217
Cdd:cd10293     3 YQAKQWLFFqASGQGPYWGQ-AGWFNVFHAEKVPSAIERYTNEIRRVLGVLETALAERyrVWLVGDKFTIADLAFVPW-- 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1755442227 218 NLIIGGLYEASKFLQVDEYKNVKRWAEEVAQRPAVQRG 255
Cdd:cd10293    80 NNVVDMIFIDPELDIKKEFPHVYKWLKRMLARPAVKKA 117

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227  45 LQLYSLGT-PNGQKVTILLEELlalgisGAEYDAHLIRISEGDQFSsgFVEVNPNSKIPALLDRSVTpavrVFESGAILL 123
Cdd:cd00570     1 LKLYYFPGsPRSLRVRLALEEK------GLPYELVPVDLGEGEQEE--FLALNPLGKVPVLEDGGLV----LTESLAILE 68

                  ...
gi 1755442227 124 YLA 126
Cdd:cd00570    69 YLA 71

C-terminal, alpha helical domain of an unknown subfamily 2 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 138 AGRAEALNWLFWLQGS-APYLGGGFGHFYHYAP-QKIEYAINRFTMEAKRQLDVLDRQLAQHRFIAGDAYSIADIAI--- 212
Cdd:cd03180     1 AQRALADRWMDWQTSTlNPAFRYAFWGLVRTPPeQRDPAAIAASLAACNKLMAILDAQLARQAYLAGDRFTLADIALgcs 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1755442227 213 -WPWYGnliigglyeaskfLQVD--EYKNVKRWAEEVAQRPA 251
Cdd:cd03180    81 vYRWLE-------------LPIErpALPHLERWYARLSQRPA 109

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227  92 FVEVNPNSKIPALL--DRSVtpavrVFESGAILLYLADKFG--QFL-PEDYAGRAEALNWLFWLqgsAPYLGGGFGHFYH 166
Cdd:PRK10542   43 YLAINPKGQVPALLldDGTL-----LTEGVAIMQYLADSVPdrQLLaPVGSLSRYHTIEWLNYI---ATELHKGFTPLFR 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 167 Y-APQkiEY-AINRFTMEakRQLDVLDRQLAQHRFIAGDAYSIADiaiwpwygnliiGGLYEASKF-----LQVDEYKNV 239
Cdd:PRK10542  115 PdTPE--EYkPTVRAQLE--KKFQYVDEALADEQWICGQRFTIAD------------AYLFTVLRWayavkLNLEGLEHI 178

                         170
                  ....*....|....
gi 1755442227 240 KRWAEEVAQRPAVQ 253
Cdd:PRK10542  179 AAYMQRVAERPAVA 192

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 1755442227 138 AGRAEALNWLFWLQGSapyLGGGFGHFYHyaPQKieYAINRFTMEAK--------RQLDVLDRQLAQHRFIAGDAYSIAD 209
Cdd:cd03188     1 LERARLLEWLNFIASE---LHKAFGPLFY--PAR--WADDALAEEVKaaarerleRRLAYLDAQLAGGPYLLGDQFSVAD 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1755442227 210 -----IAIWpwygnliigglyeaSKFLQVD--EYKNVKRWAEEVAQRPAVQR 254
Cdd:cd03188    74 aylfvVLRW--------------ARAVGLDlsDWPHLAAYLARVAARPAVQA 111

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 1755442227 146 WLFWLQGSAPYLGGGFGHFYHYAPQKIEYAINRFTMEAKRQLDVLDRQLAQHRFIAGDAYSIADIAIWPWYGNLIIGGLY 225
Cdd:cd00299     4 LEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEALGPY 83

                          90
                  ....*....|....*....
gi 1755442227 226 EASKflqvDEYKNVKRWAE 244
Cdd:cd00299    84 YDLL----DEYPRLKAWYD 98

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 1755442227  44 PLQLYS-LGTPNGQKVTILLEELlalgisGAEYDAHLIRISEGDQFSSGFVEVNPNSKIPALLDRSVTpavrVFESGAIL 122
Cdd:pfam02798   2 VLTLYGiRGSPRAHRIRWLLAEK------GVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKK----LTESRAIL 71

                  ....*
gi 1755442227 123 LYLAD 127
Cdd:pfam02798  72 EYIAR 76

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1755442227 175 AINRFTMEAKRQLDVLDRQLAQHRFIAGDAYSIADIAIWPWYGNLIIGGLYeaskFLQVDEYKNVKRWAEE 245
Cdd:pfam13410   1 ALERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPG----LDLREGYPRLRAWLER 67

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1755442227 182 EAKRQLDVLDRQLAQHRFIAGDAYSIADIAIWPWygnliIGGLYEASKFLQVDEYKNVKRWAEEVAQRP 250
Cdd:pfam00043  30 KVARVLSALEEVLKGQTYLVGDKLTLADIALAPA-----LLWLYELDPACLREKFPNLKAWFERVAARP 93

C-terminal, alpha helical domain of an unknown subfamily 5 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 5; composed of uncharacterized bacterial proteins with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 165 YHYAPQKIEYAinrftmEAKRQLDVLDRQLAQHRFIAGDAYSIADIAIWP-----------WygnliigglyeaskFLQv 233
Cdd:cd03196    34 YPEDDEEEYRA------QAEEFLAELEARLSQHAYLFGDRPSLADYAIFPfvrqfahvdrdW--------------FDA- 92

                  ....*....
gi 1755442227 234 DEYKNVKRW 242
Cdd:cd03196    93 SPYPNLRRW 101

Glutathione S-transferase C-terminal-like, alpha helical domain of Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 3; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein (AIMP) 3 subfamily; AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex that functions as a molecular hub to coordinate protein synthesis. There are three AIMPs, named AIMP1-3, which play diverse regulatory roles. AIMP3, also called p18 or eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1), contains a C-terminal domain with similarity to the C-terminal alpha helical domain of GSTs. It specifically interacts with methionyl-tRNA synthetase (MetRS) and is translocated to the nucleus during DNA synthesis or in response to DNA damage and oncogenic stress. In the nucleus, it interacts with ATM and ATR, which are upstream kinase regulators of p53. It appears to work against DNA damage in cooperation with AIMP2, and similar to AIMP2, AIMP3 is also a haploinsufficient tumor suppressor. AIMP3 transgenic mice have shorter lifespans than wild-type mice and they show characteristics of progeria, suggesting that AIMP3 may also be involved in cellular and organismal aging.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 140 RAEALNWLfwlqgsapylgggfghfyHYAPQKIEYAINRFtmEAKRQLDVLDRQLAQHRFIAGDAYSIADIAIwpWYGnl 219
Cdd:cd10305     4 RAQVDQWL------------------EYRVTQVAPASDKA--DAKSLLKELNSYLQDRTYLVGHKLTLADVVL--YYG-- 59

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1755442227 220 iIGGLYEASKFLQVDEYKNVKRWAEEVAQRPAVQRGR 256
Cdd:cd10305    60 -LHPIMKDLSPQEKEQYLNVSRWFDHVQHLPGIRQHL 95

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 1755442227  54 NGQKVTILLEELlalgisGAEYDahliRISEGDQFSS----GFVEVNPNSKIPALLDRSVTpavrVFESGAILLYLA 126
Cdd:cd03047    11 NVQKVLWLLDEL------GLPYE----RIDAGGQFGGldtpEFLAMNPNGRVPVLEDGDFV----LWESNAILRYLA 73

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 141 AEALNWLFWL---QGSA-PYL---------GGGFGHFYHYAPQKIEYAIN--RFTMEAKRQLDVLDRQLAQHRFIAGDAY 205
Cdd:cd03189     6 AEYADYLYWLhfaEGSLmPPLllklvfgkiGEAPPPFFRPISRKIADKPLqaFINPELKRHLDFLEDHLAKHPYFAGDEL 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1755442227 206 SIADIAIWpwygnLIIGGLYEASKFLQvdEYKNVKRWAEEVAQRP 250
Cdd:cd03189    86 TAADIMMS-----FPLEAALARGPLLE--QYPNIAAYLERIEARP 123

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1755442227 181 MEAKRQLDVLDRQLAQHR--FIAGDAYSIADIAIWPWYGNLIIGGLyEASKFLQVDEYKNVKRWAEEVAQRPAVQ 253
Cdd:cd03184    35 EELRSALENLEEELAKRGtpFFGGNSPGMVDYMIWPWFERLEALKL-LDGYELCLDRFPKLKKWMAAMKQDPAVK 108

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 143 ALNWLFWLQGSAPYLgggfghfyhyaPQKIEYAINrftmEAKRQLDVLDRQLAQHRFIAGDAYSIADIAIwpwYGNLIIG 222
Cdd:cd03181    20 AATWVLPLLGIAPYN-----------KKAVDKAKE----DLKRALGVLEEHLLTRTYLVGERITLADIFV---ASALLRG 81

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1755442227 223 glYE---ASKFLQvdEYKNVKRWAEEVAQRPAVQ 253
Cdd:cd03181    82 --FEtvlDPEFRK--KYPNVTRWFNTVVNQPKFK 111

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1755442227 161 FGHFYHYAPQKIEYAINRFTME--AKRQLDVLDRQLAQH--RFIAGDAYSIADIAIWpwygNLIIGGLYEASKFLqVDEY 236
Cdd:pfam14497   7 IASSLYYEDEKKKAKRRKEFREerLPKFLGYFEKVLNKNggGYLVGDKLTYADLALF----QVLDGLLYPKAPDA-LDKY 81

                          90
                  ....*....|....*..
gi 1755442227 237 KNVKRWAEEVAQRPAVQ 253
Cdd:pfam14497  82 PKLKALHERVAARPNIK 98

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1755442227 187 LDVLDRQLAQHRFIAGDAYSIADIAIWPWYGNLIIGGlYEASKflqvdeYKNVKRWAEEVAQRPA 251
Cdd:cd03177    47 LEFLETFLEGSDYVAGDQLTIADLSLVATVSTLEVVG-FDLSK------YPNVAAWYERLKALPP 104