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 1017366851  51 DQAWVDATTDLYKDFFEVFRKMIRARRnklpADELAKLTSEILIPARHPYFEILNGILERNKSGYLVGDDITLADLAISE 130
Cdd:cd03192     2 EEARVDAIVDTIADLRAEFAPYFYEPD----GEEKKEKKKEFLEEALPKFLGKFEKILKKSGGGYFVGDKLTWADLALFD 77

                          90       100
                  ....*....|....*....|....*..
gi 1017366851 131 NVDSLKNYG-LFKAEEQPKLAALREKV 156
Cdd:cd03192    78 VLDYLLYLLpKDLLEKYPKLKALRERV 104

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 1017366851  51 DQAWVDATTDLYKDFFEVFRKMIRARRnklpADELAKLTSEILIPARHPYFEILNGILERNKSGYLVGDDITLADLAISE 130
Cdd:cd03192     2 EEARVDAIVDTIADLRAEFAPYFYEPD----GEEKKEKKKEFLEEALPKFLGKFEKILKKSGGGYFVGDKLTWADLALFD 77

                          90       100
                  ....*....|....*....|....*..
gi 1017366851 131 NVDSLKNYG-LFKAEEQPKLAALREKV 156
Cdd:cd03192    78 VLDYLLYLLpKDLLEKYPKLKALRERV 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017366851  28 IPQSGAINSYLARKFG---FAGKTAKDQAWVD-----ATTDLYKDFFEVFRKMIRARRNKLPADELAKLtseilipARHp 99
Cdd:COG0625    63 LTESLAILEYLAERYPeppLLPADPAARARVRqwlawADGDLHPALRNLLERLAPEKDPAAIARARAEL-------ARL- 134

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1017366851 100 yFEILNGILErnKSGYLVGDDITLADLAISENVDSLKNYGlFKAEEQPKLAALREKVYSHSALKNYIA 167
Cdd:COG0625   135 -LAVLEARLA--GGPYLAGDRFSIADIALAPVLRRLDRLG-LDLADYPNLAAWLARLAARPAFQRALA 198

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 1017366851  51 DQAWVDATTDLYKDFFEVFRKMIRARRnklpADELAKLTSEILIPARHPYFEILNGILERNKSGYLVGDDITLADLAISE 130
Cdd:cd03192     2 EEARVDAIVDTIADLRAEFAPYFYEPD----GEEKKEKKKEFLEEALPKFLGKFEKILKKSGGGYFVGDKLTWADLALFD 77

                          90       100
                  ....*....|....*....|....*..
gi 1017366851 131 NVDSLKNYG-LFKAEEQPKLAALREKV 156
Cdd:cd03192    78 VLDYLLYLLpKDLLEKYPKLKALRERV 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1017366851  28 IPQSGAINSYLARKFG---FAGKTAKDQAWVD-----ATTDLYKDFFEVFRKMIRARRNKLPADELAKLtseilipARHp 99
Cdd:COG0625    63 LTESLAILEYLAERYPeppLLPADPAARARVRqwlawADGDLHPALRNLLERLAPEKDPAAIARARAEL-------ARL- 134

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1017366851 100 yFEILNGILErnKSGYLVGDDITLADLAISENVDSLKNYGlFKAEEQPKLAALREKVYSHSALKNYIA 167
Cdd:COG0625   135 -LAVLEARLA--GGPYLAGDRFSIADIALAPVLRRLDRLG-LDLADYPNLAAWLARLAARPAFQRALA 198

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 1017366851  61 LYKDFFEVFRKMIRaRRNKLPADELAKLTSEiliparhpyFEILNGILERNKsgYLVGDDITLADLAISENVDSLKNYGl 140
Cdd:cd03177    17 LYQRLRDYYYPILF-GGAEPPEEKLDKLEEA---------LEFLETFLEGSD--YVAGDQLTIADLSLVATVSTLEVVG- 83

                          90
                  ....*....|....*.
gi 1017366851 141 FKAEEQPKLAALREKV 156
Cdd:cd03177    84 FDLSKYPNVAAWYERL 99

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 1017366851  79 KLPADELAKLTSEILIPARHPYFEILNGILERNKsgYLVGDDITLADLAISENVDSLKNYGL-FKAEEQPKLAALREKVY 157
Cdd:pfam00043  13 YVPPEEKKEPEVDEALEKVARVLSALEEVLKGQT--YLVGDKLTLADIALAPALLWLYELDPaCLREKFPNLKAWFERVA 90

                  ..
gi 1017366851 158 SH 159
Cdd:pfam00043  91 AR 92

C-terminal, alpha helical domain of Class Theta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 the 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 the aryl or alkyl sulfate esters.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1017366851 108 LERNKsgYLVGDDITLADL-AISENVdSLK--NYGLFkaEEQPKLAALREKV 156
Cdd:cd03183    62 LKDKP--FLAGDEISIADLsAICEIM-QPEaaGYDVF--EGRPKLAAWRKRV 108