C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45446434  92 HKRAKVREIVEIICSGIQPLQNLIVL------IHVGEEKKKEWAQHWITRGFRAVEKALSTSAGKYCVGDEISMADCCLV 165
Cdd:cd03191   2 KKRARVRAIALIIACDIHPLQNLRVLkyltekLGVSEEEKLAWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICLV 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 45446434 166 PQVFNARRFHVDLRPYPIILRIDRELESNPAFRAAHPSNQ 205
Cdd:cd03191  82 PQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45446434   18 VRIAMNLKEIPYDIKPISLikSGGEQHCNEYREVNPMEQVPALQIDGHTLIESVAIMHYLEETRPQ---RPLLPQDVHKR 94
Cdd:PRK15113  22 AFVALQEKGLPFELKTVDL--DAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAPpawERIYPADLQAR 99

                 ....*.
gi 45446434   95 AKVREI 100
Cdd:PRK15113 100 ARARQI 105

C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45446434  92 HKRAKVREIVEIICSGIQPLQNLIVL------IHVGEEKKKEWAQHWITRGFRAVEKALSTSAGKYCVGDEISMADCCLV 165
Cdd:cd03191   2 KKRARVRAIALIIACDIHPLQNLRVLkyltekLGVSEEEKLAWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICLV 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 45446434 166 PQVFNARRFHVDLRPYPIILRIDRELESNPAFRAAHPSNQ 205
Cdd:cd03191  82 PQVYNARRFGVDLSPYPTIVRINEACLELPAFQAAHPENQ 121

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 45446434   4 PILYSYWRSSCSWRVRIAMNLKEIPYDIKPISLIKsgGEQHCNEYREVNPMEQVPALQIDGHTLIESVAIMHYLE 78
Cdd:cd03042   1 MILYSYFRSSASYRVRIALNLKGLDYEYVPVNLLK--GEQLSPAYRALNPQGLVPTLVIDGLVLTQSLAIIEYLD 73

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45446434   18 VRIAMNLKEIPYDIKPISLikSGGEQHCNEYREVNPMEQVPALQIDGHTLIESVAIMHYLEETRPQ---RPLLPQDVHKR 94
Cdd:PRK15113  22 AFVALQEKGLPFELKTVDL--DAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAPpawERIYPADLQAR 99

                 ....*.
gi 45446434   95 AKVREI 100
Cdd:PRK15113 100 ARARQI 105

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45446434    12 SSCSWRVRIAMNLKEIPYDIKPISLIksgGEQHCNEYREVNPMEQVPALQ-IDGHTLIESVAIMHYLEET 80
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELVDLD---PKDKPPELLALNPLGTVPVLVlPDGTVLTDSLVILEYLEEL 68

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 45446434   4 PILYSYWRSSCSWRVRIAMNLKEIPYDIKPISLikSGGEQHCNEYREVNPMEQVPALQIDGHTLIESVAIMHYLEE 79
Cdd:cd03053   2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDL--TKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAE 75

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 45446434   6 LYsYWRSSCSWRVRIAMNLKEIPYDIKPISLikSGGEQHCNEYREVNPMEQVPALQI-DGHTLIESVAIMHYLEETRP 82
Cdd:cd03057   3 LY-YSPGACSLAPHIALEELGLPFELVRVDL--RTKTQKGADYLAINPKGQVPALVLdDGEVLTESAAILQYLADLHP 77

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 45446434     5 ILYSYWRSSCSWRVRIAMNLKEIPYDIKPISLIKsgGEQHCNEYREVNPMEQVPALQIDGHTLIESVAIMHYLEE 79
Cdd:pfam02798   4 TLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGA--GPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

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
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 45446434  18 VRIAMNLKEIPYDIKPISLIKsgGEQHCNEYREVNPMEQVPALQIDGHTLIESVAIMHYL 77
Cdd:cd03050  15 VYIFLKLNKIPFEECPIDLRK--GEQLTPEFKKINPFGKVPAIVDGDFTLAESVAILRYL 72

glutathionine S-transferase; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 45446434   47 EYREVNPMEQVPALQIDGHTLI-ESVAIMHYLEETRPQRPLLP 88
Cdd:PRK10542  42 DYLAINPKGQVPALLLDDGTLLtEGVAIMQYLADSVPDRQLLA 84

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 45446434  97 VREIVEIICSGIQPLQNLIVLIHVG----EEKKKEWAQHWITRGFRAVEKALSTsaGKYCVGDEISMADCCLVPQVFNAR 172
Cdd:cd00299   1 VRALEDWADATLAPPLVRLLYLEKVplpkDEAAVEAAREELPALLAALEQLLAG--RPYLAGDQFSLADVALAPVLARLE 78

                        90
                ....*....|...
gi 45446434 173 RFHV---DLRPYP 182
Cdd:cd00299  79 ALGPyydLLDEYP 91

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 45446434   5 ILYSYWRSSCSWRVRIAMNLKEIPYDIKPISLIKSGgeqhcNEYREVNPM-EQVPALQIDGHTLIESVAIMHYLEET 80
Cdd:cd03058   2 KLLGAWASPFVLRVRIALALKGVPYEYVEEDLGNKS-----ELLLASNPVhKKIPVLLHNGKPICESLIIVEYIDEA 73

C-terminal, alpha helical domain of Class Beta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Beta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they are involved in the protection against oxidative stress and are able to bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs, contributing to antibiotic resistance. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH. One member of this subfamily is a GST from Burkholderia xenovorans LB400 that is encoded by the bphK gene and is part of the biphenyl catabolic pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45446434 121 GEEKKKEWAQHWITRGFRAVEKALStsAGKYCVGDEISMADCCLVPQVFNARRFHVDLRPYPIILRIDRELESNPAFRAA 200
Cdd:cd03188  35 LAEEVKAAARERLERRLAYLDAQLA--GGPYLLGDQFSVADAYLFVVLRWARAVGLDLSDWPHLAAYLARVAARPAVQAA 112

                .
gi 45446434 201 H 201
Cdd:cd03188 113 L 113

stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45446434   50 EVNPMEQVPALQIDGHTLIESVAIMHYLEETRPQRPLLPQDVHKRAKVREIVEIICSGIQPLQNLIVlihVGEEKKKEWA 129
Cdd:PRK09481  52 DLNPYQSVPTLVDRELTLYESRIIMEYLDERFPHPPLMPVYPVARGESRLMMHRIEKDWYSLMNKIV---NGSASEADAA 128

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 45446434  130 QHWITRGFRAVEKALSTSAgkYCVGDEISMADCCLVP 166
Cdd:PRK09481 129 RKQLREELLAIAPVFGEKP--YFMSEEFSLVDCYLAP 163

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.

                        10        20
                ....*....|....*....|....*
gi 45446434  53 PMEQVPALQIDGHTLIESVAIMHYL 77
Cdd:cd03039  46 PFGQLPVLEIDGKKLTQSNAILRYL 70

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 45446434   6 LYSYWRSSCSWRVRIAMNLKEIPYDIKPISLiksggEQHCNEYREVNPMEQVPALQIDGHTLIESVAIMHYLEE 79
Cdd:cd03059   3 LYSGPDDVYSHRVRIVLAEKGVSVEIIDVDP-----DNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDE 71

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
                ....*....|....*....|....*....
gi 45446434  51 VNPMEQVPALQI-DGHTLIESVAIMHYLE 78
Cdd:cd03049  45 VNPLGKIPALVLdDGEALFDSRVICEYLD 73

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 45446434  14 CSW--RVRIAMNLKEIPYDIKPISLIKSGgeqhcNEYREVNPMEQVPALQID-GHTLIESVAIMHYLE 78
Cdd:cd03055  27 CPYaqRARLVLAAKNIPHEVININLKDKP-----DWFLEKNPQGKVPALEIDeGKVVYESLIICEYLD 89

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
                ....*....|....*....|....*....|....*....|....
gi 45446434 122 EEKKKEWAQHWITRGFRAVEKALSTSAGKYCVGDEISMADCCLV 165
Cdd:cd03192  33 KEKKKEFLEEALPKFLGKFEKILKKSGGGYFVGDKLTWADLALF 76