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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622960840  96 LKKILDELEKVLDQVETELQRRneetpeegqqPWLCGESFTLADVSLAVTLHRLKFLGFARRNWgngkrPNLETYYERVL 175
Cdd:COG0625   124 IARARAELARLLAVLEARLAGG----------PYLAGDRFSIADIALAPVLRRLDRLGLDLADY-----PNLAAWLARLA 188

                  ....*....
gi 1622960840 176 KRKTFNKVL 184
Cdd:COG0625   189 ARPAFQRAL 197

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622960840  52 RSQIGNTESELKKL---AEENpDLQEAYIAKQKRLKSKLLDHDNVKY--LKKILDELEKVLDQVETELQRRNEE 120
Cdd:TIGR04523 116 KEQKNKLEVELNKLekqKKEN-KKNIDKFLTEIKKKEKELEKLNNKYndLKKQKEELENELNLLEKEKLNIQKN 188

C-terminal, alpha helical domain of Ganglioside-induced differentiation-associated protein 1-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ganglioside-induced differentiation-associated protein 1 (GDAP1)-like subfamily; GDAP1 was originally identified as a highly expressed gene at the differentiated stage of GD3 synthase-transfected cells. More recently, mutations in GDAP1 have been reported to cause both axonal and demyelinating autosomal-recessive Charcot-Marie-Tooth (CMT) type 4A neuropathy. CMT is characterized by slow and progressive weakness and atrophy of muscles. Sequence analysis of GDAP1 shows similarities and differences with GSTs; it appears to contain both N-terminal thioredoxin-fold and C-terminal alpha helical domains of GSTs, however, it also contains additional C-terminal transmembrane domains unlike GSTs. GDAP1 is mainly expressed in neuronal cells and is localized in the mitochondria through its transmembrane domains. It does not exhibit GST activity using standard substrates.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622960840  70 PDLQEAYIAKQKRLKSKLLDHDNVKYLKKILDELEKVLDQVETELQRRNEETPEEGQQPWLCGESFTLADVSLAVTLHRL 149
Cdd:cd03204     1 PDLAEAYTAKQKKLAIQLRDHEDSSYLKKILDELEVVLDQVEKELGERKRETDESGQQQWLCGESFTAADISLSVLLHRL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1622960840 150 KFLGFARRNWGNGKRPNLETYYERVLKRKTF 180
Cdd:cd03204    81 KFLGLSRRFWGNGKRPNIESYFERVRQRESF 111

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 1622960840  75 AYIAKQKRLKSKLLDHDNVKYLKKILDELEKVLDQVETELQrrneetpeegQQPWLCGESFTLADVSLAVTLHRLKFLGF 154
Cdd:cd00299    13 APPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLA----------GRPYLAGDQFSLADVALAPVLARLEALGP 82

                          90       100
                  ....*....|....*....|
gi 1622960840 155 ARRNWgnGKRPNLETYYERV 174
Cdd:cd00299    83 YYDLL--DEYPRLKAWYDRL 100

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622960840  96 LKKILDELEKVLDQVETELqrrneetpeeGQQPWLCGESFTLADVSLAVTLHRLKFLGFArRNWgNGKRPNLETYYER 173
Cdd:pfam13410   2 LERAREQLRAALDALEARL----------ADGPGLLGDRPTLADIALAPVLARLDAAYPG-LDL-REGYPRLRAWLER 67

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 1622960840  90 HDNVKylKKILDELEKVLDQVETELQRRneetpeegqqPWLCGESFTLADVSLAVTLHRLKFLGFARRNWgngkrPNLET 169
Cdd:cd03188    36 AEEVK--AAARERLERRLAYLDAQLAGG----------PYLLGDQFSVADAYLFVVLRWARAVGLDLSDW-----PHLAA 98

                          90
                  ....*....|....*
gi 1622960840 170 YYERVLKRKTFNKVL 184
Cdd:cd03188    99 YLARVAARPAVQAAL 113

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 1622960840  89 DHDNVKYLKKILDELEKVLdqvetelqrrneetpeeGQQPWLCGESFTLADVSLAVTLHRLKFLGFARRNWgngkrPNLE 168
Cdd:cd03177    36 PEEKLDKLEEALEFLETFL-----------------EGSDYVAGDQLTIADLSLVATVSTLEVVGFDLSKY-----PNVA 93

                  ....*...
gi 1622960840 169 TYYERVLK 176
Cdd:cd03177    94 AWYERLKA 101

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 1622960840  91 DNVKYLKKILDE-LEKVLDQVETELQRRNeetpeegqQPWLCGESFTLADVSLAVTLHRLKFLGFarrNWGNGKRPNLET 169
Cdd:cd03192    31 EKKEKKKEFLEEaLPKFLGKFEKILKKSG--------GGYFVGDKLTWADLALFDVLDYLLYLLP---KDLLEKYPKLKA 99

                  ....*
gi 1622960840 170 YYERV 174
Cdd:cd03192   100 LRERV 104

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622960840  96 LKKILDELEKVLDQVETE-LQRRneetpeegqqPWLCGESFTLADVSLAVTLHRLKFLGfaRRNWGNgkRPNLETYYERV 174
Cdd:cd03183    43 VKKAEENLEESLDLLENKfLKDK----------PFLAGDEISIADLSAICEIMQPEAAG--YDVFEG--RPKLAAWRKRV 108

                  ...
gi 1622960840 175 LKR 177
Cdd:cd03183   109 KEA 111

C-terminal, alpha helical domain of Class Omega-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae Omega-like subfamily; composed of three Saccharomyces cerevisiae GST omega-like (Gto) proteins, Gto1p, Gto2p (also known as Extracellular mutant protein 4 or ECM4p), and Gto3p, as well as similar uncharacterized proteins from fungi and bacteria. The three Saccharomyces cerevisiae Gto proteins are omega-class GSTs with low or no GST activity against standard substrates, but have glutaredoxin/thiol oxidoreductase and dehydroascorbate reductase activity through a single cysteine residue in the active site. Gto1p is located in the peroxisomes while Gto2p and Gto3p are cytosolic. The gene encoding Gto2p, called ECM4, is involved in cell surface biosynthesis and architecture. S. cerevisiae ECM4 mutants show increased amounts of the cell wall hexose, N-acetylglucosamine. More recently, global gene expression analysis shows that ECM4 is upregulated during genotoxic conditions and together with the expression profiles of 18 other genes could potentially differentiate between genotoxic and cytotoxic insults in yeast.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1622960840  91 DNVKYLKKILDELEKVLdqvetelqrrneetpeeGQQPWLCGESFTLADVSLAVTLHR 148
Cdd:cd03190    37 KAVKELFEALDKLEKRL-----------------SKQPYLLGDRLTEADIRLFTTLIR 77

C-terminal, alpha helical domain of an unknown subfamily 6 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 6; composed of uncharacterized bacterial proteins with similarity to GSTs, including Pseudomonas fluorescens GST with a known three-dimensional structure. 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. Though the three-dimensional structure of Pseudomonas fluorescens GST has been determined, there is no information on its functional characterization.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1622960840 124 EGQQPWLCGESFTLADVSLAVTLHRLKFLgFARRNWGNGkRPNLETYYERVLKRKTF 180
Cdd:cd03205    50 EAELGDLPGGRLTLGDIAVACALGYLDFR-FPELDWRAG-HPALAAWFARFEARPSF 104

C-terminal, alpha helical domain of Stringent starvation protein A; Glutathione S-transferase (GST) C-terminal domain 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 thioredoxin-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622960840  82 RLKSKLLDHDNVKYLKKILDELEKVLDQVETELQRRN--EE----TPEEGQQPWLCGESFTLADVSLAVTLHRLKFLGFa 155
Cdd:cd03186     4 RARSRLMMHRIEQDWYPLLDTILNGRDEKEAEKARKElrESltalAPVFAASPYFLSEEFSLVDCYLAPLLWRLPALGI- 82

                          90       100
                  ....*....|....*....|....*....
gi 1622960840 156 rrNWGNGKRPnLETYYERVLKRKTFNKVL 184
Cdd:cd03186    83 --ELPKQAKA-IKDYMERVFARDSFQASL 108

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622960840  52 RSQIGNTESELKKL---AEENpDLQEAYIAKQKRLKSKLLDHDNVKY--LKKILDELEKVLDQVETELQRRNEE 120
Cdd:TIGR04523 116 KEQKNKLEVELNKLekqKKEN-KKNIDKFLTEIKKKEKELEKLNNKYndLKKQKEELENELNLLEKEKLNIQKN 188

C-terminal, alpha helical domain of GTT2-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the Saccharomyces 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 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. 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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1622960840 126 QQPWLCGESFTLADVSLAVtlhrlkFLGFARrnwgNGK------RPNLETYYERVLKR 177
Cdd:cd03182    66 ESPYVAGDRFSIADITAFV------ALDFAK----NLKlpvpeeLTALRRWYERMAAR 113