C-terminal, alpha helical domain of Class Phi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Tau 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787  94 LERASIEQWLQAEAQSFDAPSSELVFHLAFAPQLNIPADEARIAENERKLQQMLNVYDEILAKNKYLAGDEFTLADLSHL 173
Cdd:cd03187     1 KERALVEQWLEVEAHQFDPPASKLVFELVFKPMLGLKTDEAVVEENEAKLKKVLDVYEARLSKSKYLAGDSFTLADLSHL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1002249787 174 PNSHYIVNARSprgKKLFTSKKHVARWYEEISNRASWKQVV 214
Cdd:cd03187    81 PNLHYLMATPS---KKLFDSRPHVKAWWEDISARPAWKKVL 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1002249787   3 AGLQVFGQPASTDVARVLTCLFEKNLEFELIRIDTFKKEHKLPEFIKLRdPTGQV-TFKHGDKTLVDSRAICRYL 76
Cdd:pfam02798   1 MVLTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLN-PLGKVpALEDGGKKLTESRAILEYI 74

C-terminal, alpha helical domain of Class Phi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Tau 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787  94 LERASIEQWLQAEAQSFDAPSSELVFHLAFAPQLNIPADEARIAENERKLQQMLNVYDEILAKNKYLAGDEFTLADLSHL 173
Cdd:cd03187     1 KERALVEQWLEVEAHQFDPPASKLVFELVFKPMLGLKTDEAVVEENEAKLKKVLDVYEARLSKSKYLAGDSFTLADLSHL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1002249787 174 PNSHYIVNARSprgKKLFTSKKHVARWYEEISNRASWKQVV 214
Cdd:cd03187    81 PNLHYLMATPS---KKLFDSRPHVKAWWEDISARPAWKKVL 118

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787   5 LQVFGQPASTDVARVLTCLFEKNLEFELIRIDTFKKEHKLPEFIKLrDPTGQV-TFKHGDKTLVDSRAICRYLSTQFPDD 83
Cdd:COG0625     2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKGEQKSPEFLAL-NPLGKVpVLVDDGLVLTESLAILEYLAERYPEP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787  84 GnrtIYGTGSLERASIEQWLQAEAQSFDAPSSELVFHlaFAPQlnipADEARIAENERKLQQMLNVYDEILAKNKYLAGD 163
Cdd:COG0625    81 P---LLPADPAARARVRQWLAWADGDLHPALRNLLER--LAPE----KDPAAIARARAELARLLAVLEARLAGGPYLAGD 151

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1002249787 164 EFTLADLSHLPNSHYIvnarsPRGKKLFTSKKHVARWYEEISNRASWKQVV 214
Cdd:COG0625   152 RFSIADIALAPVLRRL-----DRLGLDLADYPNLAAWLARLAARPAFQRAL 197

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 1002249787   5 LQVFGQPASTDVARVLTCLFEKNLEFELIRIDTFKKEHKlpEFIKLRdPTGQV-TFKHGDKTLVDSRAICRYL 76
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQE--EFLALN-PLGKVpVLEDGGLVLTESLAILEYL 70

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 1002249787  95 ERASIEQWLQAEAQSFDAPSSELVFHLAFAPQLNIPADEARIAENERklqqMLNVYDEILAKNKYLAGDEFTLADLSHLP 174
Cdd:cd03178     1 ERAEVLQWLFFQMSGLGPMFGQAGHFLYFAPEKIPYAIERYTDEVKR----LYGVLDKRLSDRPYLAGEEYSIADIALYP 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1002249787 175 NSHYIVNArsprGKKLFTSKKHVARWYEEISNR 207
Cdd:cd03178    77 WTHYADLG----GFADLSEYPNVKRWLERIAAR 105

glutathionine S-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787  23 LFEKNLEFELIRIDTFKKEHKLPEFIKLRDPTGQV-TFKHGDKT-LVDSRAICRYLSTQFPDdgNRTIYGTGSLERASIE 100
Cdd:PRK10542   18 LRESGLDFTLVSVDLAKKRLENGDDYLAINPKGQVpALLLDDGTlLTEGVAIMQYLADSVPD--RQLLAPVGSLSRYHTI 95

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1002249787 101 QWLqaeaqSFDApsSELvfHLAFAPQLN--IPADEARIAENerKLQQMLNVYDEILAKNKYLAGDEFTLAD 169
Cdd:PRK10542   96 EWL-----NYIA--TEL--HKGFTPLFRpdTPEEYKPTVRA--QLEKKFQYVDEALADEQWICGQRFTIAD 155

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 1002249787  95 ERASIEQWLQAEAQSFDAPSSELVFHLAFAPqlniPA--DEARIAENERKLQQMLNVYDEILAKNKYLAGDEFTLAD--L 170
Cdd:cd03180     2 QRALADRWMDWQTSTLNPAFRYAFWGLVRTP----PEqrDPAAIAASLAACNKLMAILDAQLARQAYLAGDRFTLADiaL 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1002249787 171 SHLPNSHY---IVNARSPrgkklftskkHVARWYEEISNRA 208
Cdd:cd03180    78 GCSVYRWLelpIERPALP----------HLERWYARLSQRP 108

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1002249787 132 DEARIAENERKLQQMLNVYDEILAKNKYLAGDEFTLADLSHLP--NSHYIvnarsPRGKKLFTSKKHVARWYEEISNR 207
Cdd:pfam00043  20 KEPEVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIALAPalLWLYE-----LDPACLREKFPNLKAWFERVAAR 92

GST_N family, Class Theta subfamily; composed of eukaryotic class Theta GSTs and bacterial dichloromethane (DCM) dehalogenase. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Mammalian class Theta GSTs show poor GSH conjugating activity towards the standard substrates, CDNB and ethacrynic acid, differentiating them from other mammalian GSTs. GSTT1-1 shows similar cataytic activity as bacterial DCM dehalogenase, catalyzing the GSH-dependent hydrolytic dehalogenation of dihalomethanes. This is an essential process in methylotrophic bacteria to enable them to use chloromethane and DCM as sole carbon and energy sources. The presence of polymorphisms in human GSTT1-1 and its relationship to the onset of diseases including cancer is subject of many studies. Human GSTT2-2 exhibits a highly specific sulfatase activity, catalyzing the cleavage of sulfate ions from aralkyl sufate esters, but not from aryl or alkyl sulfate esters.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1002249787   5 LQVFGQPASTDVARVLTCLFEKNLEFELIRIDTFKKEHKLPEFIKLrDPTGQV-TFKHGDKTLVDSRAICRYLSTQF 80
Cdd:cd03050     1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRKGEQLTPEFKKI-NPFGKVpAIVDGDFTLAESVAILRYLARKF 76

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 1002249787  99 IEQWLQAEAQSFDAPSSELVFHLAFAPqlniPADEARIAENERKLQQMLNVYDEILAKNKYLAGDEFTLADLSHLPNSHY 178
Cdd:cd00299     1 VRALEDWADATLAPPLVRLLYLEKVPL----PKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLAR 76

                          90       100
                  ....*....|....*....|....
gi 1002249787 179 IVnaRSPRGKKLFTSKKHVARWYE 202
Cdd:cd00299    77 LE--ALGPYYDLLDEYPRLKAWYD 98

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1002249787   8 FGQPASTDVARVLTCLFEKNLEFELIRIDTFkkeHKLPEFIKLrDPTGQV-TFKHGDKTLVDSRAICRYLSTQFPD 82
Cdd:pfam13417   2 YGFPGSPYARRVRIALNEKGLPYEFVPIPPG---DHPPELLAK-NPLGKVpVLEDDGGILCESLAIIDYLEELYPG 73

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787 140 ERKLQqmLNVYDEILAKNKYLAGDEFTLADLSHLPNSHYIVNARSPRGKKLFTSK--KHVARWYEEISNR 207
Cdd:cd10292    44 EAKRQ--LDVLDRQLATHKYLAGDEYTIADMAIWPWYGGLALGSLYDAAEFLDVDeyKHVQRWAKDIAAR 111

GST_N family, unknown subfamily 4; 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1002249787  28 LEFELIRIDTFKKEHKLPEFIKLrDPTGQV-TFKHGDKTLVDSRAICRYLS 77
Cdd:cd03056    24 IPYEWVEVDILKGETRTPEFLAL-NPNGEVpVLELDGRVLAESNAILVYLA 73

C-terminal, alpha helical domain of Class Theta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 the 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 the aryl or alkyl sulfate esters.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787  95 ERASIEQWLQAEAQSFDAPSSELVFHLAFAPQL-NIPADEARIAENERKLQQMLNVYDEI-LAKNKYLAGDEFTLADLSh 172
Cdd:cd03183     1 KRARVDEYLAWQHTNLRLGCAAYFWQKVLLPLFgGTPVSPEKVKKAEENLEESLDLLENKfLKDKPFLAGDEISIADLS- 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1002249787 173 lpnshYIVNARSPR--GKKLFTSKKHVARWYEEISNRASW 210
Cdd:cd03183    80 -----AICEIMQPEaaGYDVFEGRPKLAAWRKRVKEAGNP 114

putative S-transferase; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787 140 ERKLQqmLNVYDEILAKNKYLAGDEFTLADLSHLPNSHYIVNARSPRGKKLFT--SKKHVARWYEEISNR 207
Cdd:PRK11752  182 EAKRQ--LDVLDKQLAEHEYIAGDEYTIADIAIWPWYGNLVLGNLYDAAEFLDvgSYKHVQRWAKEIAER 249

C-terminal, alpha helical domain of an unknown subfamily 8 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 8; composed of Agrobacterium tumefaciens GST and other 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. The three-dimensional structure of Agrobacterium tumefaciens GST has been determined but there is no information on its functional characterization.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787 101 QWLQAEAQSFDAPSSELVFHLAFAPqlniPADEARIAENERKLQQMLNVYDEILAKNKYLAGDEFTLADL 170
Cdd:cd03207     3 RWLFFAAGTVEPPLLNKALGRFFEP----PWGEPAIAAAYGDLDERLAALEAALAGRPYLVGERFSAADL 68

GST_N family, Class Zeta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor. They show little GSH-conjugating activity towards traditional GST substrates but display modest GSH peroxidase activity. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1002249787  13 STDVARVLTCLFEKNLEFELIRIDTFKKEHKLPEFIKLrDPTGQV-TFKHGDKTLVDSRAICRYL 76
Cdd:cd03042     9 SSASYRVRIALNLKGLDYEYVPVNLLKGEQLSPAYRAL-NPQGLVpTLVIDGLVLTQSLAIIEYL 72

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787 140 ERKLQQMLNVYDEILAKN--KYLAGDEFTLADLSHLpnsHYIVNARSPRGKKLFTSKKHVARWYEEISNR 207
Cdd:pfam14497  28 EERLPKFLGYFEKVLNKNggGYLVGDKLTYADLALF---QVLDGLLYPKAPDALDKYPKLKALHERVAAR 94

Glutathione S-transferase C-terminal-like, alpha helical domain of various Aminoacyl-tRNA synthetases and similar domains; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl-tRNA synthetase (AaRS)-like subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of some eukaryotic AaRSs, as well as similar domains found in proteins involved in protein synthesis including Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 2 (AIMP2), AIMP3, and eukaryotic translation Elongation Factor 1 beta (eEF1b). AaRSs comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. AaRSs in this subfamily include GluRS from lower eukaryotes, as well as GluProRS, MetRS, and CysRS from higher eukaryotes. AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex found in higher eukaryotes. The GST_C-like domain is involved in protein-protein interactions, mediating the formation of aaRS complexes such as the MetRS-Arc1p-GluRS ternary complex in lower eukaryotes and the multi-aaRS complex in higher eukaryotes, that act as molecular hubs for protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002249787 127 LNIPADEARIAENERKLQQmLNVYdeiLAKNKYLAGDEFTLADL---SHLpnsHYIVNARSPRGKKLFtskKHVARWYEE 203
Cdd:cd10289     9 LDLAGSLLKGKELEALLKS-LNSY---LASRTFLVGYSLTLADVavfSAL---YPSGQKLSDKEKKKF---PHVTRWFNH 78

                  ...
gi 1002249787 204 ISN 206
Cdd:cd10289    79 IQN 81

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 1002249787  94 LERASIEQWLqaeaqSFdaPSSELvfHLAFAPQLNiPADEARIAENER-------KLQQMLNVYDEILAKNKYLAGDEFT 166
Cdd:cd03188     1 LERARLLEWL-----NF--IASEL--HKAFGPLFY-PARWADDALAEEvkaaareRLERRLAYLDAQLAGGPYLLGDQFS 70

                  ...
gi 1002249787 167 LAD 169
Cdd:cd03188    71 VAD 73

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1002249787 136 IAENERKLQQMLNVYDEILAKNKYLAGDEFTLADLSHLPNSHYIVNArsPRGKKLFTSKKHVARWYEE 203
Cdd:pfam13410   2 LERAREQLRAALDALEARLADGPGLLGDRPTLADIALAPVLARLDAA--YPGLDLREGYPRLRAWLER 67