Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold; The thioredoxin (TRX)-like superfamily is a large, diverse group of proteins containing a TRX fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include the families of TRX, protein disulfide isomerase (PDI), tlpA, glutaredoxin, NrdH redoxin, and bacterial Dsb proteins (DsbA, DsbC, DsbG, DsbE, DsbDgamma). Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins, glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 300360534   1 MRFCPFAERTRLVLKAKGIRHEVININLKNKPEWFFKKNPFGLVPVLENSQGQLIYESAITCEYLD 66
Cdd:cd03055   24 MRFCPYAQRARLVLAAKNIPHEVININLKDKPDWFLEKNPQGKVPALEIDEGKVVYESLIICEYLD 89

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 300360534   1 MRFCPFAERTRLVLKAKGIRHEVININLKNKPEWFFKKNPFGLVPVLENSQGQLIYESAITCEYLD 66
Cdd:cd03055   24 MRFCPYAQRARLVLAAKNIPHEVININLKDKPDWFLEKNPQGKVPALEIDEGKVVYESLIICEYLD 89

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 300360534    3 FCPFAERTRLVLKAKGIRHEV--ININLKNKPEWFFKKNPFGLVPVLENSQGQLIYESAITCEYLDEA 68
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLPYEIelVDLDPKDKPPELLALNPLGTVPVLVLPDGTVLTDSLVILEYLEEL 68

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300360534   4 CPFAERTRLVLKAKGIRHEVININLKNKPEWFFKKNPFGLVPVLENSQgQLIYESAITCEYLDEAYPGKKLlpDDPYEKA 83
Cdd:PLN02817  73 CPFCQRVLLTLEEKHLPYDMKLVDLTNKPEWFLKISPEGKVPVVKLDE-KWVADSDVITQALEEKYPDPPL--ATPPEKA 149

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 300360534  84 cqkmilELFSKVPSLVGSFIRSQNKEDyaGLKEEFRKEFTKLEEVLTNKKtTFFGGNSISMIDYLIWPWFERLE 157
Cdd:PLN02817 150 ------SVGSKIFSTFIGFLKSKDPGD--GTEQALLDELTSFDDYIKENG-PFINGEKISAADLSLGPKLYHLE 214

putative glutathione S-transferase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 300360534   5 PFAERTRLVLKAKGIRHEVININLKNKPEWFFKKNPFGLVPVLENSQGQLIYESAITCEYLDEAYPGKKLLPDDP 79
Cdd:PRK10357  10 PFVRKISILLLEKGITFEFVNELPYNADNGVAQYNPLGKVPALVTEEGECWFDSPIIAEYIELLNVAPAMLPRDP 84

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 300360534   1 MRFCPFAERTRLVLKAKGIRHEVININLKNKPEWFFKKNPFGLVPVLENSQGQLIYESAITCEYLD 66
Cdd:cd03055   24 MRFCPYAQRARLVLAAKNIPHEVININLKDKPDWFLEKNPQGKVPALEIDEGKVVYESLIICEYLD 89

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 300360534    3 FCPFAERTRLVLKAKGIRHEV--ININLKNKPEWFFKKNPFGLVPVLENSQGQLIYESAITCEYLDEA 68
Cdd:pfam13409   1 FSPFSHRVRLALEEKGLPYEIelVDLDPKDKPPELLALNPLGTVPVLVLPDGTVLTDSLVILEYLEEL 68

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 300360534   1 MRFCPFAERTRLVLKAKGIRHEVININLKNKPEWFFKK-NPFGLVPVLENSqGQLIYESAITCEYLD 66
Cdd:cd00570    6 FPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFLAlNPLGKVPVLEDG-GLVLTESLAILEYLA 71

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300360534   4 CPFAERTRLVLKAKGIRHEVININLKNKPEWFFKKNPFGLVPVLENSQgQLIYESAITCEYLDEAYPGKKLlpDDPYEKA 83
Cdd:PLN02817  73 CPFCQRVLLTLEEKHLPYDMKLVDLTNKPEWFLKISPEGKVPVVKLDE-KWVADSDVITQALEEKYPDPPL--ATPPEKA 149

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 300360534  84 cqkmilELFSKVPSLVGSFIRSQNKEDyaGLKEEFRKEFTKLEEVLTNKKtTFFGGNSISMIDYLIWPWFERLE 157
Cdd:PLN02817 150 ------SVGSKIFSTFIGFLKSKDPGD--GTEQALLDELTSFDDYIKENG-PFINGEKISAADLSLGPKLYHLE 214

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 300360534    1 MRFCPFAERTRLVLKAKGIRHEVININLK---NKPEWFFKKNPFGLVPVLENsQGQLIYESAITCEYLDE 67
Cdd:pfam02798   8 IRGSPRAHRIRWLLAEKGVEYEIVPLDFGagpEKSPELLKLNPLGKVPALED-GGKKLTESRAILEYIAR 76

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 300360534   1 MRFCPFAERTRLVLKAKGIRHEVININLK---NKPEWFFKKNPFGLVPVLENSqGQLIYESAITCEYLDE 67
Cdd:cd03053    7 AAMSTCVRRVLLCLEEKGVDYELVPVDLTkgeHKSPEHLARNPFGQIPALEDG-DLKLFESRAITRYLAE 75

GST_N family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT2. 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. GTT2, a homodimer, exhibits GST activity with standard substrates. Strains with deleted GTT2 genes are viable but exhibit increased sensitivity to heat shock.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 300360534   5 PFAERTRLVLKAKGIRHEVININL---KNKPEWFFKKNPFGLVPVLENSQGQLIYESAITCEYLD 66
Cdd:cd03051   10 PNPRRVRIFLAEKGIDVPLVTVDLaagEQRSPEFLAKNPAGTVPVLELDDGTVITESVAICRYLE 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 300360534 115 KEEFRKEFTKLEEVLtnKKTTFFGGNSISMIDYLIWPWFERLEAMKLNECV-DHTPKLKLWMAAM 178
Cdd:cd00299   38 REELPALLAALEQLL--AGRPYLAGDQFSLADVALAPVLARLEALGPYYDLlDEYPRLKAWYDRL 100

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 300360534   5 PFAERTRLVL--KAKGIRHEVININLKNKPEWFFKKNPFGLVPVLENSQGQLIYESAITCEYLD 66
Cdd:cd03049   10 PYVRKVRVAAheTGLGDDVELVLVNPWSDDESLLAVNPLGKIPALVLDDGEALFDSRVICEYLD 73

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300360534  12 LVLKAKGIRHEVININLKNKP----EWFFKKNPFGLVPVLENSQGQLIYESAITCEYLDEAYPGKKLLPddPYEKACQKM 87
Cdd:PRK10542  16 ITLRESGLDFTLVSVDLAKKRlengDDYLAINPKGQVPALLLDDGTLLTEGVAIMQYLADSVPDRQLLA--PVGSLSRYH 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300360534  88 ILELFSKVPSLV----GSFIRSQNKEDY-AGLKEEFRKEFTKLEEVLTNKKttFFGGNSISMID-YLI----WPwferlE 157
Cdd:PRK10542  94 TIEWLNYIATELhkgfTPLFRPDTPEEYkPTVRAQLEKKFQYVDEALADEQ--WICGQRFTIADaYLFtvlrWA-----Y 166

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 300360534 158 AMKLN-ECVDHtpkLKLWMAAMKEDPTVSALLTSEK 192
Cdd:PRK10542 167 AVKLNlEGLEH---IAAYMQRVAERPAVAAALKAEG 199

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 300360534   9 RTRLVLKAKGIRHEVININL----KNKPEwFFKKNPFGLVPVLENSqGQLIYES-AItCEYLD 66
Cdd:cd03042   14 RVRIALNLKGLDYEYVPVNLlkgeQLSPA-YRALNPQGLVPTLVID-GLVLTQSlAI-IEYLD 73

C-terminal, alpha helical domain of Class Tau Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300360534  94 KVPSLVGSFIRSQNKEDyAGLKEEFRKEFTKLEEVLTNKKTtFFGGNSISMID---YLIWPWFERLEAM---KLNEcVDH 167
Cdd:cd03185   17 KLFPAGRKVWAAKGEEQ-EKAVEEALEALKVLEEELKGGKP-FFGGDTIGYLDialGSFLGWFKAIEEVggvKLLD-EEK 93

                         90       100
                 ....*....|....*....|.
gi 300360534 168 TPKLKLWMAAMKEDPTVSALL 188
Cdd:cd03185   94 FPLLAAWAERFLEREAVKEVL 114

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300360534   4 CPfaERTRLVLKAKGIRHEVININL----KNKPEWFFKKnPFGLVPVLENSQGQLIYESAITCEYLDE-AYPGKKLLPDD 78
Cdd:PLN02473  13 NP--QRVLLCFLEKGIEFEVIHVDLdkleQKKPEHLLRQ-PFGQVPAIEDGDLKLFESRAIARYYATKyADQGTDLLGKT 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300360534  79 PYEKACQKMILEL----FSKVP-SLVGSFI---RSQNKEDYAgLKEEFRKEFTKLEEVLTNKKTT--FFGGNSISMIDYL 148
Cdd:PLN02473  90 LEHRAIVDQWVEVennyFYAVAlPLVINLVfkpRLGEPCDVA-LVEELKVKFDKVLDVYENRLATnrYLGGDEFTLADLT 168

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 300360534 149 IWPWFERL-EAMKLNECVDHTPKLKLWMAAMKEDPTVSALL 188
Cdd:PLN02473 169 HMPGMRYImNETSLSGLVTSRENLNRWWNEISARPAWKKLM 209

GST_N family, Beta etherase LigE subfamily; composed of proteins similar to Sphingomonas paucimobilis beta etherase, LigE, a GST-like protein that catalyzes the cleavage of the beta-aryl ether linkages present in low-moleculer weight lignins using GSH as the hydrogen donor. This reaction is an essential step in the degradation of lignin, a complex phenolic polymer that is the most abundant aromatic material in the biosphere. The beta etherase activity of LigE is enantioselective and it complements the activity of the other GST family beta etherase, LigF.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300360534   3 FCPFAERTRLVLKAKGIRHEVININLKNKPEWFFK--KNPFGLVPVLENSQGQLIYESAITCEYLDEAYP 70
Cdd:cd03038   15 FSPNVWKTRLALNHKGLEYKTVPVEFPDIPPILGEltSGGFYTVPVIVDGSGEVIGDSFAIAEYLEEAYP 84

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 300360534  12 LVLKAKGIRHEVININLKN----KPEwFFKKNPFGLVPVLENSqGQLIYESAITCEYL 65
Cdd:cd03045   17 LTAKALGLELNLKEVNLMKgehlKPE-FLKLNPQHTVPTLVDN-GFVLWESHAILIYL 72

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300360534   3 FCPFAERTRLVLKAKGIRHEVININLKNK----PEWFfKKNPFGLVPVLENSQGQLIYESAItCEYLDEAYPG---KKLL 75
Cdd:PRK15113  15 FSPYVMSAFVALQEKGLPFELKTVDLDAGehlqPTYQ-GYSLTRRVPTLQHDDFELSESSAI-AEYLEERFAPpawERIY 92

                         90
                 ....*....|...
gi 300360534  76 PDDPYEKACQKMI 88
Cdd:PRK15113  93 PADLQARARARQI 105

C-terminal, alpha helical domain of Escherichia coli YfcG Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YfcG-like subfamily; composed of the Escherichia coli YfcG and related proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YfcG is one of nine GST homologs in Escherichia coli. It is expressed predominantly during the late stationary phase where the predominant form of GSH is glutathionylspermidine (GspSH), suggesting that YfcG might interact with GspSH. It has very low or no GSH transferase or peroxidase activity, but displays a unique disulfide bond reductase activity that is comparable to thioredoxins (TRXs) and glutaredoxins (GRXs). However, unlike TRXs and GRXs, YfcG does not contain a redox active cysteine residue and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YcfG reveals a bound GSSG molecule in its active site. The actual physiological substrates for YfcG are yet to be identified.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 300360534 108 KEDYAglKEEFRKEFTKLEEVLTN--KKTTFFGGNSISMIDYLIWPWFERLEAMKLNecVDHTPKLKLWMAAMKEDPTV 184
Cdd:cd10291   33 KIPYA--IKRYTNETKRLYGVLDRrlAKSKYLAGDEYSIADIAIWPWVARHEWQGID--LADFPNLKRWFERLAARPAV 107

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 300360534 102 FIRSQNKEDYAGLKEEFRKE-----FTKLEEVLTNKKTTFFGGNSISMIDYLIWPWFERLEAMKLNECVDHTPKLK 172
Cdd:cd03192   23 YFYEPDGEEKKEKKKEFLEEalpkfLGKFEKILKKSGGGYFVGDKLTWADLALFDVLDYLLYLLPKDLLEKYPKLK 98

GST_N family, Gamma subunit of Elongation Factor 1B (EFB1gamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal TRX-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 300360534  30 NKPEWFFKKNPFGLVPVLENSQGQLIYESAITCEYL 65
Cdd:cd03044   37 NKTPEFLKKFPLGKVPAFEGADGFCLFESNAIAYYV 72