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 569005742  67 QQEAALVDMVNDGLEDL----FRRIARQYrhilKEGKDQYQKELPGHLKPFETLLAQNrGGQSFIVGDQISFADYRLLDV 142
Cdd:cd03210    1 EKEAALIDMVNDGVEDLrlkyVRMIYQNY----EAGKDDYIKDLPEQLKPFEKLLAKN-NGKGFIVGDKISFADYNLFDL 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 569005742 143 LLNLELLFPGYLNDFPLFSAYVARLKSRPKLKAFLESPEHVNRP 186
Cdd:cd03210   76 LDIHLVLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRP 119

C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Pi 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 Pi GST is a homodimeric eukaryotic protein. The human GSTP1 is mainly found in erythrocytes, kidney, placenta and fetal liver. It is involved in stress responses and in cellular proliferation pathways as an inhibitor of JNK (c-Jun N-terminal kinase). Following oxidative stress, monomeric GSTP1 dissociates from JNK and dimerizes, losing its ability to bind JNK and causing an increase in JNK activity, thereby promoting apoptosis. GSTP1 is expressed in various tumors and is the predominant GST in a wide range of cancer cells. It has been implicated in the development of multidrug-resistant tumors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005742  67 QQEAALVDMVNDGLEDL----FRRIARQYrhilKEGKDQYQKELPGHLKPFETLLAQNrGGQSFIVGDQISFADYRLLDV 142
Cdd:cd03210    1 EKEAALIDMVNDGVEDLrlkyVRMIYQNY----EAGKDDYIKDLPEQLKPFEKLLAKN-NGKGFIVGDKISFADYNLFDL 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 569005742 143 LLNLELLFPGYLNDFPLFSAYVARLKSRPKLKAFLESPEHVNRP 186
Cdd:cd03210   76 LDIHLVLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRP 119

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005742   2 RMLLADQGQSWKEEVVTLDVWEQGT--FKASCLFGQIPKFQDGELTLYQSNTILRHLGRSFG---LYGKDQQEAALVDMV 76
Cdd:COG0625   17 RIALEEKGLPYELVPVDLAKGEQKSpeFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPeppLLPADPAARARVRQW 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005742  77 ----NDGLEDLFRRIARQYRHIL-KEGKDQYQKELPGHLKPFETLLAqnrgGQSFIVGDQISFAD-------YRLLDVLL 144
Cdd:COG0625   97 lawaDGDLHPALRNLLERLAPEKdPAAIARARAELARLLAVLEARLA----GGPYLAGDRFSIADialapvlRRLDRLGL 172

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 569005742 145 NlellfpgyLNDFPLFSAYVARLKSRPKLKAFLESPE 181
Cdd:COG0625  173 D--------LADYPNLAAWLARLAARPAFQRALAAAE 201

glutathione s-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005742  33 FGQIPKFQDGELTLYQSNTILRHLGRSFGLYGKDQQEAALVDMVNDGLEDLFRRIARQyrHILKEGKDQY-QKELPGHLK 111
Cdd:PTZ00057  56 FEQVPILEMDNIIFAQSQAIVRYLSKKYKICGESELNEFYADMIFCGVQDIHYKFNNT--NLFKQNETTFlNEELPKWSG 133

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569005742 112 PFETLLAQNRggQSFIVGDQISFADYRLLDVLLNLELLFPGYLNDFPLFSAYVARLKSRPKLKAFL 177
Cdd:PTZ00057 134 YFENILKKNH--CNYFVGDNLTYADLAVFNLYDDIETKYPNSLKNFPLLKAHNEFISNLPNIKNYI 197

C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Pi 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 Pi GST is a homodimeric eukaryotic protein. The human GSTP1 is mainly found in erythrocytes, kidney, placenta and fetal liver. It is involved in stress responses and in cellular proliferation pathways as an inhibitor of JNK (c-Jun N-terminal kinase). Following oxidative stress, monomeric GSTP1 dissociates from JNK and dimerizes, losing its ability to bind JNK and causing an increase in JNK activity, thereby promoting apoptosis. GSTP1 is expressed in various tumors and is the predominant GST in a wide range of cancer cells. It has been implicated in the development of multidrug-resistant tumors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005742  67 QQEAALVDMVNDGLEDL----FRRIARQYrhilKEGKDQYQKELPGHLKPFETLLAQNrGGQSFIVGDQISFADYRLLDV 142
Cdd:cd03210    1 EKEAALIDMVNDGVEDLrlkyVRMIYQNY----EAGKDDYIKDLPEQLKPFEKLLAKN-NGKGFIVGDKISFADYNLFDL 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 569005742 143 LLNLELLFPGYLNDFPLFSAYVARLKSRPKLKAFLESPEHVNRP 186
Cdd:cd03210   76 LDIHLVLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRP 119

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005742   2 RMLLADQGQSWKEEVVTLDVWEQGT--FKASCLFGQIPKFQDGELTLYQSNTILRHLGRSFG---LYGKDQQEAALVDMV 76
Cdd:COG0625   17 RIALEEKGLPYELVPVDLAKGEQKSpeFLALNPLGKVPVLVDDGLVLTESLAILEYLAERYPeppLLPADPAARARVRQW 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005742  77 ----NDGLEDLFRRIARQYRHIL-KEGKDQYQKELPGHLKPFETLLAqnrgGQSFIVGDQISFAD-------YRLLDVLL 144
Cdd:COG0625   97 lawaDGDLHPALRNLLERLAPEKdPAAIARARAELARLLAVLEARLA----GGPYLAGDRFSIADialapvlRRLDRLGL 172

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 569005742 145 NlellfpgyLNDFPLFSAYVARLKSRPKLKAFLESPE 181
Cdd:COG0625  173 D--------LADYPNLAAWLARLAARPAFQRALAAAE 201

Glutathione S-transferase, C-terminal domain; This domain is closely related to pfam00043.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005742   96 KEGKDQYQKELPGHLKPFETLLAQNRGGqsFIVGDQISFADYRL-LDVLLNLELLFPGYLNDFPLFSAYVARLKSRPKLK 174
Cdd:pfam14497  21 KRRKEFREERLPKFLGYFEKVLNKNGGG--YLVGDKLTYADLALfQVLDGLLYPKAPDALDKYPKLKALHERVAARPNIK 98

                  ....*.
gi 569005742  175 AFLESP 180
Cdd:pfam14497  99 AYLASR 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 569005742  68 QEAALVDMVNDGLEDLFRRIARQYR-----HILKEGKDQYQKELPGHLKPFETLLAQNRGGqsFIVGDQISFADYrlldv 142
Cdd:cd03192    1 EEEARVDAIVDTIADLRAEFAPYFYepdgeEKKEKKKEFLEEALPKFLGKFEKILKKSGGG--YFVGDKLTWADL----- 73

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 569005742 143 llNLELLFPGYLNDFPLFSayvarLKSRPKLKAFLE 178
Cdd:cd03192   74 --ALFDVLDYLLYLLPKDL-----LEKYPKLKALRE 102

C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 Alpha subfamily is composed of vertebrate 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 569005742  67 QQEAALVDMVNDGLEDLFRRIA-----------RQYRHILKEGKDQYqkelpghLKPFETLLAQNrgGQSFIVGDQISFA 135
Cdd:cd03208    1 LKERALIDMYVEGTADLMEMIMmlpflppeekeAKLALIKEKAKNRY-------FPVFEKVLKDH--GQDFLVGNKLSRA 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 569005742 136 DYRLLDVLLNLELLFPGYLNDFPLFSAYVARLKSRPKLKAFLE 178
Cdd:cd03208   72 DVQLLEAILMVEELDPSILSDFPLLQAFKTRISNIPTIKKFLQ 114

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
                 ....*....|....*....|....*.
gi 569005742  33 FGQIPKFQDGELTLYQSNTILRHLGR 58
Cdd:cd03053   50 FGQIPALEDGDLKLFESRAITRYLAE 75

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
                  ....*....|....*....|....*....|..
gi 569005742   27 FKASCLFGQIPKFQDGELTLYQSNTILRHLGR 58
Cdd:pfam02798  45 LLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

GST_N family, unknown subfamily 2; 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. The sequence from Burkholderia cepacia was identified as part of a gene cluster involved in the degradation of 2,4,5-trichlorophenoxyacetic acid. Some GSTs (e.g. Class Zeta and Delta) are known to catalyze dechlorination reactions.

                         10        20
                 ....*....|....*....|....*
gi 569005742  33 FGQIPKFQDGELTLYQSNTILRHLG 57
Cdd:cd03047   49 NGRVPVLEDGDFVLWESNAILRYLA 73

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 569005742   91 YRHILKEGKDQYQKELPGHLKPFETLLAQNRGgQSFIVGDQISFADYRLLDVLLNLELLFPGYLND-FPLFSAYVARLKS 169
Cdd:pfam00043  13 YVPPEEKKEPEVDEALEKVARVLSALEEVLKG-QTYLVGDKLTLADIALAPALLWLYELDPACLREkFPNLKAWFERVAA 91

                  ..
gi 569005742  170 RP 171
Cdd:pfam00043  92 RP 93