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        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 835333026   6 IHYFDFPGgRAEPARIALRYAGIDFEDVRFSPKELAERA--KAYPLGKVPVMDVEGHRVTQSNAINRYVGK 74
Cdd:cd03039    3 LTYFNIRG-RGEPIRLLLADAGVEYEDVRITYEEWPELDlkPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

glutathione s-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 835333026   6 IHYFDfPGGRAEPARIALRYAGIDFEDVRFSPKELA-------ERAKAYPLGKVPVMDVEGHRVTQSNAINRYVGKLTGL 78
Cdd:PTZ00057   7 LYYFD-ARGKAELIRLIFAYLGIEYTDKRFGENGDAfiefknfKKEKDTPFEQVPILEMDNIIFAQSQAIVRYLSKKYKI 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 835333026  79 YPNDPIQALLCDEALDAAEELTAKVAETFSLQGEELKAAREKLcatvfPAYLTFFSKKLAQAG-DYFADNRLTIADLRVM 157
Cdd:PTZ00057  86 CGESELNEFYADMIFCGVQDIHYKFNNTNLFKQNETTFLNEEL-----PKWSGYFENILKKNHcNYFVGDNLTYADLAVF 160

                 ..
gi 835333026 158 ML 159
Cdd:PTZ00057 161 NL 162

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        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 835333026   6 IHYFDFPGgRAEPARIALRYAGIDFEDVRFSPKELAERA--KAYPLGKVPVMDVEGHRVTQSNAINRYVGK 74
Cdd:cd03039    3 LTYFNIRG-RGEPIRLLLADAGVEYEDVRITYEEWPELDlkPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

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 835333026    5 SIHYFDFPGG-RAEPARIALRYAGIDFEDVR----FSPKELAERAKAYPLGKVPVMDVEGHRVTQSNAINRYV 72
Cdd:pfam02798   2 VLTLYGIRGSpRAHRIRWLLAEKGVEYEIVPldfgAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYI 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 835333026   8 YFDFPGGRAEPARIALRYAGIDFEDVRFSPKELAERAKAY----PLGKVPVMDVEGHRVTQSNAINRYV 72
Cdd:cd03056    4 YGFPLSGNCYKVRLLLALLGIPYEWVEVDILKGETRTPEFlalnPNGEVPVLELDGRVLAESNAILVYL 72

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 835333026  86 ALLCDEALDAAEELTAKVAETF-SLQGEELKAAREKLCATVFPAYLTFFSKKLAQAGD-YFADNRLTIADLRVMMLLRHL 163
Cdd:cd03192    3 EARVDAIVDTIADLRAEFAPYFyEPDGEEKKEKKKEFLEEALPKFLGKFEKILKKSGGgYFVGDKLTWADLALFDVLDYL 82

                         90       100
                 ....*....|....*....|....*..
gi 835333026 164 csgaLDHVPADLVDKHaPNLQDYLQRV 190
Cdd:cd03192   83 ----LYLLPKDLLEKY-PKLKALRERV 104

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 835333026   19 ARIALRYAGIDFE--DVRFSPKELAERAKAY-PLGKVPVM-DVEGHRVTQSNAINRYVGKL 75
Cdd:pfam13409   8 VRLALEEKGLPYEieLVDLDPKDKPPELLALnPLGTVPVLvLPDGTVLTDSLVILEYLEEL 68

GST_N family, Class Alpha 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 class Alpha subfamily is composed of eukaryotic GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 835333026   3 KLSIHYFDfPGGRAEPARIALRYAGIDFEDVRFSPKELAERAK---AYPLGKVPVMDVEGHRVTQSNAINRYVGKLTGLY 79
Cdd:cd03077    1 KPVLHYFN-GRGRMESIRWLLAAAGVEFEEKFIESAEDLEKLKkdgSLMFQQVPMVEIDGMKLVQTRAILNYIAGKYNLY 79

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 835333026  21 IALRYAGIDFED--VRFSPKELAERAKAY-PLGKVPVMDVEGHRVTQSNAINRYV 72
Cdd:cd03043   18 LLLKAAGIPFEEilVPLYTPDTRARILEFsPTGKVPVLVDGGIVVWDSLAICEYL 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 835333026  19 ARIALRYAGIDFE----DVRFSPKELAERAKAYPLGKVPVMDVEGHRVTQSNAINRYV 72
Cdd:cd03053   16 VLLCLEEKGVDYElvpvDLTKGEHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYL 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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 835333026  19 ARIALRYAGIDFEDVRFSPKELAERAKAY----PLGKVPVMDVE-GHRVTQSNAI 68
Cdd:cd03057   14 PHIALEELGLPFELVRVDLRTKTQKGADYlainPKGQVPALVLDdGEVLTESAAI 68

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 835333026  112 EELKAAREKLcATVFPAYLTFFSKKlaqagDYFADNRLTIADLRVMMLLRHLcsgaLDHVPADLVDKHaPNLQDYLQRVS 191
Cdd:pfam00043  22 PEVDEALEKV-ARVLSALEEVLKGQ-----TYLVGDKLTLADIALAPALLWL----YELDPACLREKF-PNLKAWFERVA 90

                  ...
gi 835333026  192 QHE 194
Cdd:pfam00043  91 ARP 93

Glutathione S-transferase, N-terminal domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 835333026    9 FDFPGGR-AEPARIALRYAGIDFEDVRFSP-KELAERAKAYPLGKVPVMDVEGHRVTQSNAINRYV 72
Cdd:pfam13417   2 YGFPGSPyARRVRIALNEKGLPYEFVPIPPgDHPPELLAKNPLGKVPVLEDDGGILCESLAIIDYL 67