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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903  89 QKQALINQRLYFDMGTLYKSFSEYYYPQIFLKKPANEENYKKIEVAFEFLNTFLEGQTYSAGGDYSLADIAFLATVSTFD 168
Cdd:cd03177    1 KKRAIVNQRLFFDSGTLYQRLRDYYYPILFGGAEPPEEKLDKLEEALEFLETFLEGSDYVAGDQLTIADLSLVATVSTLE 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 665393903 169 VAGFDFKRYANVARWYENAKKLTPGWEENWAGCQEFR 205
Cdd:cd03177   81 VVGFDLSKYPNVAAWYERLKALPPGEEENGEGAKELK 117

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903  89 QKQALINQRLYFDMGTLYKSFSEYYYPQIFLKKPANEENYKKIEVAFEFLNTFLEGQTYSAGGDYSLADIAFLATVSTFD 168
Cdd:cd03177    1 KKRAIVNQRLFFDSGTLYQRLRDYYYPILFGGAEPPEEKLDKLEEALEFLETFLEGSDYVAGDQLTIADLSLVATVSTLE 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 665393903 169 VAGFDFKRYANVARWYENAKKLTPGWEENWAGCQEFR 205
Cdd:cd03177   81 VVGFDLSKYPNVAAWYERLKALPPGEEENGEGAKELK 117

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 665393903   1 MDLYYRPGSAPCRSVLMTAKALGVEFDKKTIiNTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYLVE 75
Cdd:cd03045    1 IDLYYLPGSPPCRAVLLTAKALGLELNLKEV-NLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

maleylacetoacetate isomerase; Maleylacetoacetate isomerase is an enzyme of tyrosine and phenylalanine catabolism. It requires glutathione and belongs by homology to the zeta family of glutathione S-transferases. The enzyme (EC 5.2.1.2) is described as active also on maleylpyruvate, and the example from a Ralstonia sp. catabolic plasmid is described as a maleylpyruvate isomerase involved in gentisate catabolism. [Energy metabolism, Amino acids and amines]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903    4 YYRPG-SAPCRsvlmTAKAL-GVEFDKKTIINTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYLVEKYgKDD 81
Cdd:TIGR01262   5 YWRSScSYRVR----IALALkGIDYEYVPVNLLRDGEQRSPEFLALNPQGLVPTLDIDGEVLTQSLAIIEYLEETY-PDP 79

                          90
                  ....*....|.
gi 665393903   82 KLFPKDVQKQA 92
Cdd:TIGR01262  80 PLLPADPIKRA 90

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903  14 SVLMTAKALGVEFDKKTIiNTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYLVEKYGKDD--KLFPKDVQKQ 91
Cdd:PRK15113  21 SAFVALQEKGLPFELKTV-DLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAPPAweRIYPADLQAR 99

                 ....*
gi 665393903  92 ALINQ 96
Cdd:PRK15113 100 ARARQ 104

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903  89 QKQALINQRLYFDMGTLYKSFSEYYYPQIFLKKPANEENYKKIEVAFEFLNTFLEGQTYSAGGDYSLADIAFLATVSTFD 168
Cdd:cd03177    1 KKRAIVNQRLFFDSGTLYQRLRDYYYPILFGGAEPPEEKLDKLEEALEFLETFLEGSDYVAGDQLTIADLSLVATVSTLE 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 665393903 169 VAGFDFKRYANVARWYENAKKLTPGWEENWAGCQEFR 205
Cdd:cd03177   81 VVGFDLSKYPNVAAWYERLKALPPGEEENGEGAKELK 117

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 665393903   1 MDLYYRPGSAPCRSVLMTAKALGVEFDKKTIiNTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYLVE 75
Cdd:cd03045    1 IDLYYLPGSPPCRAVLLTAKALGLELNLKEV-NLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLVE 74

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 665393903   3 LYYRPGSAPCRSVLMTAKALGVEFDKKTIiNTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYLVEKY 77
Cdd:cd03050    3 LYYDLMSQPSRAVYIFLKLNKIPFEECPI-DLRKGEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYLARKF 76

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903   1 MDLYYRPGSAPCRSVLMTAKAlGVEFdKKTIINTRAREQFTPEYLKINPQHTIPTLHDHG-------FALWESRAIMVYL 73
Cdd:PRK13972   2 IDLYFAPTPNGHKITLFLEEA-ELDY-RLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSpadggepLSLFESGAILLYL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903  74 VEKYGKddkLFPKDVQKQALINQRLYFDMGTLYKSFSEYYY-----PQIFlkkPANEENYK-KIEVAFEFLNTFLEGQTY 147
Cdd:PRK13972  80 AEKTGL---FLSHETRERAATLQWLFWQVGGLGPMLGQNHHfnhaaPQTI---PYAIERYQvETQRLYHVLNKRLENSPW 153

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 665393903 148 SAGGDYSLADIAFLATVSTFDVAGFDFKRYANVARWYENAK 188
Cdd:PRK13972 154 LGGENYSIADIACWPWVNAWTRQRIDLAMYPAVKNWHERIR 194

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 665393903   3 LYYRPGSapcRS--VLMTAKALGVEFDKKtIINTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYLVEKYG 78
Cdd:cd03046    3 LYHLPRS---RSfrILWLLEELGLPYELV-LYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 76

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903   1 MDLYYRPGS---APCrsvlMTAKALGVEFDKKtIINTRAREQFTPEYLKINPQHTIPTL-HDHGFALWESRAIMVYLVEK 76
Cdd:cd03057    1 MKLYYSPGAcslAPH----IALEELGLPFELV-RVDLRTKTQKGADYLAINPKGQVPALvLDDGEVLTESAAILQYLADL 75

                 .
gi 665393903  77 Y 77
Cdd:cd03057   76 H 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 665393903  94 INQRLYFDMGTLYKSFSEYYYPQIFLKKP---ANEENYKKIEVAFEFLNTFLEGQTYSAGGDYSLADIAFLATVSTFDVA 170
Cdd:cd00299    1 VRALEDWADATLAPPLVRLLYLEKVPLPKdeaAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEAL 80

                         90
                 ....*....|....*....
gi 665393903 171 G---FDFKRYANVARWYEN 186
Cdd:cd00299   81 GpyyDLLDEYPRLKAWYDR 99

Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665393903   12 CRSVLMTAKALGVEFDKKTIINTRarEQFTPEYLKINPQHTIPTLHDH-GFALWESRAIMVYL 73
Cdd:pfam13409   5 SHRVRLALEEKGLPYEIELVDLDP--KDKPPELLALNPLGTVPVLVLPdGTVLTDSLVILEYL 65

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 665393903   1 MDLY-YRPGSAPCRsvLMTAKAL-GVEFDKKTIiNTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYL 73
Cdd:cd03042    1 MILYsYFRSSASYR--VRIALNLkGLDYEYVPV-NLLKGEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYL 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 665393903   1 MDLYYRPGSAPCRSVLMTAKALGVEFDKKTIiNTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYL 73
Cdd:cd03056    1 MKLYGFPLSGNCYKVRLLLALLGIPYEWVEV-DILKGETRTPEFLALNPNGEVPVLELDGRVLAESNAILVYL 72

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903   3 LYYRPGSAPCRSVLMTAKALGVEFDKkTIINTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYLVEKYG-KDD 81
Cdd:PLN02473   5 VYGQIKAANPQRVLLCFLEKGIEFEV-IHVDLDKLEQKKPEHLLRQPFGQVPAIEDGDLKLFESRAIARYYATKYAdQGT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903  82 KLFPKDVQKQALINQrlYFDMGTLYksFSEYYYPQIF-------LKKPAN----EENYKKIEVAFEFLNTFLEGQTYSAG 150
Cdd:PLN02473  84 DLLGKTLEHRAIVDQ--WVEVENNY--FYAVALPLVInlvfkprLGEPCDvalvEELKVKFDKVLDVYENRLATNRYLGG 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 665393903 151 GDYSLADIAFLAT----VSTFDVAGFdFKRYANVARWYENAKKlTPGWEE 196
Cdd:PLN02473 160 DEFTLADLTHMPGmryiMNETSLSGL-VTSRENLNRWWNEISA-RPAWKK 207

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903   1 MDLYYRPGSapCR-SVLMTAKALGVEFdkkTIINTRAREQFTP---EYLKINPQHTIPTLH-DHGFALWESRAIMVYLVE 75
Cdd:PRK10542   1 MKLFYKPGA--CSlASHITLRESGLDF---TLVSVDLAKKRLEngdDYLAINPKGQVPALLlDDGTLLTEGVAIMQYLAD 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903  76 KygKDDK--LFPKDVQKQALINQRLYFDMGTLYKSFSEYYYPqiflKKPaneENYK-----KIEVAFEFLNTFLEGQTYS 148
Cdd:PRK10542  76 S--VPDRqlLAPVGSLSRYHTIEWLNYIATELHKGFTPLFRP----DTP---EEYKptvraQLEKKFQYVDEALADEQWI 146

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 665393903 149 AGGDYSLADiAFLATVSTFDVA-GFDFKRYANVARWYE 185
Cdd:PRK10542 147 CGQRFTIAD-AYLFTVLRWAYAvKLNLEGLEHIAAYMQ 183

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903  14 SVLMTAKALGVEFDKKTIiNTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYLVEKYGKDD--KLFPKDVQKQ 91
Cdd:PRK15113  21 SAFVALQEKGLPFELKTV-DLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAPPAweRIYPADLQAR 99

                 ....*
gi 665393903  92 ALINQ 96
Cdd:PRK15113 100 ARARQ 104

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 665393903  94 INQRLYFDMGTLYKSFSEYYYPQIF--LKKPANEENYKKiEV--AFEFLNTFLEGQTYSAGGDYSLADIAFLATVSTFDV 169
Cdd:cd03178    5 VLQWLFFQMSGLGPMFGQAGHFLYFapEKIPYAIERYTD-EVkrLYGVLDKRLSDRPYLAGEEYSIADIALYPWTHYADL 83

                         90
                 ....*....|....*..
gi 665393903 170 AGF-DFKRYANVARWYE 185
Cdd:cd03178   84 GGFaDLSEYPNVKRWLE 100

Glutathione S-transferase C-terminal-like, alpha helical domain of Glutamyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, Glutamyl-tRNA synthetase (GluRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of GluRS from lower eukaryotes. Aminoacyl-tRNA synthetases (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. The GST_C-like domain of GluRS is involved in protein-protein interactions. This domain mediates the formation of the MetRS-Arc1p-GluRS ternary complex found in lower eukaryotes, which is considered an evolutionary intermediate between prokaryotic aaRS and the multi-aaRS complex found in higher eukaryotes. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 665393903 127 NYKKIEVAFEFLNTFLEGQTYSAGGDYSLADIAFLATVSTFDVAGFDFKR--YANVARWY 184
Cdd:cd10306   22 DFKALSQALEELDSHLTLRTFIVGYSLSLADIAVWGALRGNGVAGSLIKNkvYVNLSRWF 81

stringent starvation protein A; Provisional

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 665393903  43 EYLKINPQHTIPTLHDHGFALWESRAIMVYLVEKY 77
Cdd:PRK09481  49 DLIDLNPYQSVPTLVDRELTLYESRIIMEYLDERF 83

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 665393903 129 KKIEVAFEFLNTFLEGQTYSAGGDYSLADIAFLATVSTFDVAGFDFKR--YANVARWY 184
Cdd:cd10289   19 KELEALLKSLNSYLASRTFLVGYSLTLADVAVFSALYPSGQKLSDKEKkkFPHVTRWF 76

GST_N family, unknown subfamily 1; composed of uncharacterized proteins, predominantly from bacteria, with similarity to GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains.

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gi 665393903  19 AKALGVEFDkkTIINTRAREQFTPEYLKINPQHTIPTLHDHGFALWESRAIMVYL 73
Cdd:cd03043   20 LKAAGIPFE--EILVPLYTPDTRARILEFSPTGKVPVLVDGGIVVWDSLAICEYL 72

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.

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gi 665393903  113 YYPQIFLKKPANEENYKKIEVAFEFLNTFLEGQTYSAGGDYSLADIAFLATVSTFDVAGFDFKR--YANVARWYEN 186
Cdd:pfam00043  13 YVPPEEKKEPEVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIALAPALLWLYELDPACLRekFPNLKAWFER 88

GST_N family, unknown subfamily 3; 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.

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gi 665393903   1 MDLYYRPGSAPCRSVLMTA--KALGVEFDKKTIiNTRAREqftPEYLKINPQHTIPTL-HDHGFALWESRAIMVYL 73
Cdd:cd03049    1 MKLLYSPTSPYVRKVRVAAheTGLGDDVELVLV-NPWSDD---ESLLAVNPLGKIPALvLDDGEALFDSRVICEYL 72