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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFG---QPAWYREISPLGRIPALRDGDLALADSSVICQYLEERYPEPP 79
Cdd:COG0625    2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKgeqKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEPP 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  80 nLQGDAPASRAAVRWLEKYADYEIAPLatLTIFRNRILKPamgqacEENDVRRALEEKLPAHFDYLENHLDGRAFFVGER 159
Cdd:COG0625   82 -LLPADPAARARVRQWLAWADGDLHPA--LRNLLERLAPE------KDPAAIARARAELARLLAVLEARLAGGPYLAGDR 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 489205730 160 LTLADLAIASQLVNLRHAGENLDEqrWPALAAHFARMLERPAMQALLPGERRTLD 214
Cdd:COG0625  153 FSIADIALAPVLRRLDRLGLDLAD--YPNLAAWLARLAARPAFQRALAAAEPDLA 205

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFG---QPAWYREISPLGRIPALRDGDLALADSSVICQYLEERYPEPP 79
Cdd:COG0625    2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKgeqKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEPP 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  80 nLQGDAPASRAAVRWLEKYADYEIAPLatLTIFRNRILKPamgqacEENDVRRALEEKLPAHFDYLENHLDGRAFFVGER 159
Cdd:COG0625   82 -LLPADPAARARVRQWLAWADGDLHPA--LRNLLERLAPE------KDPAAIARARAELARLLAVLEARLAGGPYLAGDR 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 489205730 160 LTLADLAIASQLVNLRHAGENLDEqrWPALAAHFARMLERPAMQALLPGERRTLD 214
Cdd:COG0625  153 FSIADIALAPVLRRLDRLGLDLAD--YPNLAAWLARLAARPAFQRALAAAEPDLA 205

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 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPF-GQPAWYREISPLGRIPALRDGDLALADSSVICQYLE 72
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGeGEQEEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFG---QPAWYREISPLGRIPALRDGDLALADSSVICQYLEERYPEPP 79
Cdd:COG0625    2 MKLYGSPPSPNSRRVRIALEEKGLPYELVPVDLAKgeqKSPEFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPEPP 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  80 nLQGDAPASRAAVRWLEKYADYEIAPLatLTIFRNRILKPamgqacEENDVRRALEEKLPAHFDYLENHLDGRAFFVGER 159
Cdd:COG0625   82 -LLPADPAARARVRQWLAWADGDLHPA--LRNLLERLAPE------KDPAAIARARAELARLLAVLEARLAGGPYLAGDR 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 489205730 160 LTLADLAIASQLVNLRHAGENLDEqrWPALAAHFARMLERPAMQALLPGERRTLD 214
Cdd:COG0625  153 FSIADIALAPVLRRLDRLGLDLAD--YPNLAAWLARLAARPAFQRALAAAEPDLA 205

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 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPF-GQPAWYREISPLGRIPALRDGDLALADSSVICQYLE 72
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGeGEQEEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

GST_N family, Class Phi subfamily; composed of plant-specific class Phi GSTs and related fungal and bacterial proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Phi GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Tau GSTs, showing class specificity in substrate preference. Phi enzymes are highly reactive toward chloroacetanilide and thiocarbamate herbicides. Some Phi GSTs have other functions including transport of flavonoid pigments to the vacuole, shoot regeneration and GSH peroxidase activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFG---QPAWYREISPLGRIPALRDGDLALADSSVICQYLEER 74
Cdd:cd03053    2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKgehKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

putative glutathione S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730   5 LYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFGQPAWYREISPLGRIPAL-RDGDLALADSSVICQYLEERYPEPPNLQG 83
Cdd:PRK10357   3 LIGSYTSPFVRKISILLLEKGITFEFVNELPYNADNGVAQYNPLGKVPALvTEEGECWFDSPIIAEYIELLNVAPAMLPR 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  84 DaPASRAAVRWLEKYADYEIAplATLTIFRNRiLKPAmGQACEENDVRRalEEKLPAHFDYLENHL-DGRafFVGERLTL 162
Cdd:PRK10357  83 D-PLAALRVRQLEALADGIMD--AALVSVREQ-ARPA-AQQSEDELLRQ--REKINRSLDALEGYLvDGT--LKTDTVNL 153

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 489205730 163 ADLAIASQL--VNLRHAGENLDEQRwPALAAHFARMLER 199
Cdd:PRK10357 154 ATIAIACAVgyLNFRRVAPGWCVDR-PHLVKLVENLFQR 191

stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFGQPAWYREISPLGRIPALRDGDLALADSSVICQYLEERYPEPPnLQ 82
Cdd:PRK09481  11 MTLFSGPTDIYSHQVRIVLAEKGVSVEIEQVEKDNLPQDLIDLNPYQSVPTLVDRELTLYESRIIMEYLDERFPHPP-LM 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  83 GDAPASRAAVRWLEKYADYEIAPLAtltifrNRILKpamGQACEENDVRRALEEKLPAhfdyLENHLDGRAFFVGERLTL 162
Cdd:PRK09481  90 PVYPVARGESRLMMHRIEKDWYSLM------NKIVN---GSASEADAARKQLREELLA----IAPVFGEKPYFMSEEFSL 156

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 489205730 163 ADLAIASQLVNLRHAGENLDEQRWPALAAHFARMLERPAMQALLPGERR 211
Cdd:PRK09481 157 VDCYLAPLLWRLPVLGIELSGPGAKELKGYMTRVFERDSFLASLTEAER 205

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  12 PFVRKVRLLLAEKGLDYQLEAIAPFGQPAWYREISPLGRIPALRDGDLALADSSVICQYLEERYPEPPNlqgDAPASRAA 91
Cdd:PLN02817  74 PFCQRVLLTLEEKHLPYDMKLVDLTNKPEWFLKISPEGKVPVVKLDEKWVADSDVITQALEEKYPDPPL---ATPPEKAS 150

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  92 VrwlekyadyeiaplatltifRNRILKPAMG--QACEEND-VRRALEEKLPAHFDYLEnhlDGRAFFVGERLTLADLAIA 168
Cdd:PLN02817 151 V--------------------GSKIFSTFIGflKSKDPGDgTEQALLDELTSFDDYIK---ENGPFINGEKISAADLSLG 207

                 ....*....
gi 489205730 169 SQLVNLRHA 177
Cdd:PLN02817 208 PKLYHLEIA 216

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 489205730   3 LTLYGAPLSPFVRkVRLLLAEKGLDYQLEAI---APFGQPAWYREISPLGRIPALRDGDLALADSSVICQYLEERYP 76
Cdd:cd03046    1 ITLYHLPRSRSFR-ILWLLEELGLPYELVLYdrgPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 76

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 489205730    1 MSLTLYGAPLSPFVRKVRLLLAEKGLDYQ---LEAIAPFGQPAWYREISPLGRIPALRDGDLALADSSVICQYLEE 73
Cdd:pfam02798   1 MVLTLYGIRGSPRAHRIRWLLAEKGVEYEivpLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIA-PFG--QPAWYREISPLGRIPALRDGDLALADSSVICQYL 71
Cdd:cd03047    1 LTIWGRRSSINVQKVLWLLDELGLPYERIDAGgQFGglDTPEFLAMNPNGRVPVLEDGDFVLWESNAILRYL 72

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFG---QPAWYREISPLGRIPALRDGDLALADSSVICQYL 71
Cdd:cd03056    1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEVDILKgetRTPEFLALNPNGEVPVLELDGRVLAESNAILVYL 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 489205730 129 DVRRALEEKLPAHFDYLENHLDGRAFFVGERLTLADlAIASQLVNLRHAGEnLDEQRWPALAAHFARMLERPAMQALL 206
Cdd:cd03188   38 EVKAAARERLERRLAYLDAQLAGGPYLLGDQFSVAD-AYLFVVLRWARAVG-LDLSDWPHLAAYLARVAARPAVQAAL 113

C-terminal, alpha helical domain of Class Sigma-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi, and Alpha. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal 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. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation, and mediation of allergy and inflammation. Other class Sigma-like members include the class II insect GSTs, S-crystallins from cephalopods, nematode-specific GSTs, and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase, and PGD2 synthase activities, and may play an important role in host-parasite interactions. Members also include novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730 107 ATLTIFRNRILKPAMGQACEENDVRRA--LEEKLPAHFDYLENHL--DGRAFFVGERLTLADLAIASQLVNLRHAGENLD 182
Cdd:cd03192   11 DTIADLRAEFAPYFYEPDGEEKKEKKKefLEEALPKFLGKFEKILkkSGGGYFVGDKLTWADLALFDVLDYLLYLLPKDL 90

                         90
                 ....*....|....
gi 489205730 183 EQRWPALAAHFARM 196
Cdd:cd03192   91 LEKYPKLKALRERV 104

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  21 LAEKGLDYQLEAI----APFGQPAWYREISPLGRIPALR--DGDLaLADSSVICQYLEERYPEPPNLQGDAPASR-AAVR 93
Cdd:PRK10542  18 LRESGLDFTLVSVdlakKRLENGDDYLAINPKGQVPALLldDGTL-LTEGVAIMQYLADSVPDRQLLAPVGSLSRyHTIE 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  94 WLeKYADYEI----APLatltiFRNRI---LKPAmgqaceendVRRALEEKlpahFDYLENHLDGRAFFVGERLTLADla 166
Cdd:PRK10542  97 WL-NYIATELhkgfTPL-----FRPDTpeeYKPT---------VRAQLEKK----FQYVDEALADEQWICGQRFTIAD-- 155

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 489205730 167 iASQLVNLRHA-GENLDEQRWPALAAHFARMLERPAMQALLPGE 209
Cdd:PRK10542 156 -AYLFTVLRWAyAVKLNLEGLEHIAAYMQRVAERPAVAAALKAE 198

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 489205730   2 SLTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFGQPAWYREISPLGRIPALR-DGDLALADSSVICQYLE 72
Cdd:cd03055   18 IIRLYSMRFCPYAQRARLVLAAKNIPHEVININLKDKPDWFLEKNPQGKVPALEiDEGKVVYESLIICEYLD 89

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFG----QPAwYREISPLGRIPALRDGDLALADSSVICQYLEE 73
Cdd:cd03045    1 IDLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKgehlKPE-FLKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 489205730  134 LEEKLPAHFDYLENHL--DGRAFFVGERLTLADLAIASQLVNLRHAGENLDEQRWPALAAHFARMLERPAMQA 204
Cdd:pfam14497  27 REERLPKFLGYFEKVLnkNGGGYLVGDKLTYADLALFQVLDGLLYPKAPDALDKYPKLKALHERVAARPNIKA 99

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFG----QPAwYREISPLGRIPALRDGDLALADSSVICQYLE 72
Cdd:cd03042    1 MILYSYFRSSASYRVRIALNLKGLDYEYVPVNLLKgeqlSPA-YRALNPQGLVPTLVIDGLVLTQSLAIIEYLD 73

GST_N family, Class Beta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit limited GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they also bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 489205730   3 LTLYGAPLS-PFVrkVRLLLAEKGLDYQLEAIAPFGQPAW---YREISPLGRIPALRDGD-LALADSSVICQYLEERYP 76
Cdd:cd03057    1 MKLYYSPGAcSLA--PHIALEELGLPFELVRVDLRTKTQKgadYLAINPKGQVPALVLDDgEVLTESAAILQYLADLHP 77

C-terminal, alpha helical domain of an unknown subfamily 6 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 6; composed of uncharacterized bacterial proteins with similarity to GSTs, including Pseudomonas fluorescens GST with a known three-dimensional structure. 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. Though the three-dimensional structure of Pseudomonas fluorescens GST has been determined, there is no information on its functional characterization.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 489205730 135 EEKLPAHFDYLENHLDGRAffvGERLTLADLAIASQL--VNLRHAGENlDEQRWPALAAHFARMLERPAMQALLP 207
Cdd:cd03205   39 WGKIERALDALEAELGDLP---GGRLTLGDIAVACALgyLDFRFPELD-WRAGHPALAAWFARFEARPSFQATPP 109

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 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFGQPA---WYREISPLGRIPALRDGDLALADSSVICQYLEERY 75
Cdd:cd03050    1 LKLYYDLMSQPSRAVYIFLKLNKIPFEECPIDLRKGEQltpEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

GST_N family, Class Tau 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 plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 489205730   3 LTLYGAPLSPFVRKVRLLLAEKGLDYQLEAIAPFGQPAWYREISPL-GRIPALRDGDLALADSSVICQYLEE 73
Cdd:cd03058    1 VKLLGAWASPFVLRVRIALALKGVPYEYVEEDLGNKSELLLASNPVhKKIPVLLHNGKPICESLIIVEYIDE 72

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730 138 LPAHFDYLENHL---DGRAFFVGERLTLADLAIASQLVNLRH-AGENLDEqrWPALAAHFARMLERPAMQALLpgERRTL 213
Cdd:cd03210   40 LPEQLKPFEKLLaknNGKGFIVGDKISFADYNLFDLLDIHLVlAPGCLDA--FPLLKAFVERLSARPKLKAYL--ESDAF 115

                 ...
gi 489205730 214 DKL 216
Cdd:cd03210  116 KNR 118

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.

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                 ....*....|....*....|....*....|....*....|.
gi 489205730 135 EEKLPAHFDYLENHLDGRAFFVGERLTLADLAIASQLVNLR 175
Cdd:cd10289   18 GKELEALLKSLNSYLASRTFLVGYSLTLADVAVFSALYPSG 58

C-terminal, alpha helical domain of an unknown subfamily 7 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 7; composed of uncharacterized 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 489205730 128 NDVRRALEEklpAH--FDYLENHLDGRAFFVGERLTLADLAIASQLVnlrHAGE-NLDEQRWPALAAHFAR 195
Cdd:cd03206   29 LDPERARAI---SHrlLRLLDQHLAGRDWLAGDRPTIADVACYPYIA---LAPEgGVSLEPYPAIRAWLAR 93

GST_N family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi and Alpha. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation and mediation of allergy and inflammation. Other class Sigma members include the class II insect GSTs, S-crystallins from cephalopods and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase and PGD2 synthase activities, and may play an important role in host-parasite interactions. Also members are novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 489205730  17 VRLLLAEKGLDYQLEAIAPFGQPAWYREIS-PLGRIPALRDGDLALADSSVICQYL 71
Cdd:cd03039   15 IRLLLADAGVEYEDVRITYEEWPELDLKPTlPFGQLPVLEIDGKKLTQSNAILRYL 70

glutathione s-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  17 VRLLLAEKGLDY-------QLEAIAPFGQPAWYREiSPLGRIPALRDGDLALADSSVICQYLEERYpeppNLQGDAPASr 89
Cdd:PTZ00057  19 IRLIFAYLGIEYtdkrfgeNGDAFIEFKNFKKEKD-TPFEQVPILEMDNIIFAQSQAIVRYLSKKY----KICGESELN- 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489205730  90 aavrwlEKYADYEIAPLATLTI-FRNRILkpamgqaCEENDVrRALEEKLPAHFDYLENHL--DGRAFFVGERLTLADLA 166
Cdd:PTZ00057  93 ------EFYADMIFCGVQDIHYkFNNTNL-------FKQNET-TFLNEELPKWSGYFENILkkNHCNYFVGDNLTYADLA 158

                 .
gi 489205730 167 I 167
Cdd:PTZ00057 159 V 159