C-terminal, alpha helical domain of Escherichia coli Yghu Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YghU-like subfamily; composed of the Escherichia coli YghU and related 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. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YghU is one of nine GST homologs in the genome of Escherichia coli. It is similar to Escherichia coli YfcG in that it has poor GSH transferase activity towards typical substrates. It shows modest reductase activity towards some organic hydroperoxides. Like YfcG, YghU also shows good disulfide bond oxidoreductase activity comparable to the activities of glutaredoxins and thioredoxins. YghU does not contain a redox active cysteine residue, and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YghU reveals two GSH molecules bound in its active site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270 140 RTETLNWLFWQMGSAPYVGGGFGHFYAYAPEKFEYPINRFTMETKRQLDVLNRQLAENRYLAGDSYTIADIAVWPWYGGL 219
Cdd:cd10292    2 RTETLNWLFWQMGSAPYLGGGFGHFYSYAPVKIEYAIDRFTMEAKRQLDVLDRQLATHKYLAGDEYTIADMAIWPWYGGL 81

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 741126270 220 VQNALYSAGEFLSVHEYEHVIRWADEIAARPAVIRGR 256
Cdd:cd10292   82 ALGSLYDAAEFLDVDEYKHVQRWAKDIAARPAVKRGR 118

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 741126270   65 LLALGHSGAEYDAWLIKIGDGDQFSSGFVDVNPNSKIPALLDqsGEKPIrvFESGSILVYLAE 127
Cdd:pfam02798  18 RWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALED--GGKKL--TESRAILEYIAR 76

C-terminal, alpha helical domain of Escherichia coli Yghu Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YghU-like subfamily; composed of the Escherichia coli YghU and related 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. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YghU is one of nine GST homologs in the genome of Escherichia coli. It is similar to Escherichia coli YfcG in that it has poor GSH transferase activity towards typical substrates. It shows modest reductase activity towards some organic hydroperoxides. Like YfcG, YghU also shows good disulfide bond oxidoreductase activity comparable to the activities of glutaredoxins and thioredoxins. YghU does not contain a redox active cysteine residue, and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YghU reveals two GSH molecules bound in its active site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270 140 RTETLNWLFWQMGSAPYVGGGFGHFYAYAPEKFEYPINRFTMETKRQLDVLNRQLAENRYLAGDSYTIADIAVWPWYGGL 219
Cdd:cd10292    2 RTETLNWLFWQMGSAPYLGGGFGHFYSYAPVKIEYAIDRFTMEAKRQLDVLDRQLATHKYLAGDEYTIADMAIWPWYGGL 81

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 741126270 220 VQNALYSAGEFLSVHEYEHVIRWADEIAARPAVIRGR 256
Cdd:cd10292   82 ALGSLYDAAEFLDVDEYKHVQRWAKDIAARPAVKRGR 118

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270  45 LQLYSLATPNGVKVTIMLEEllalghSGAEYDAWLIKIGDGDQFSSGFVDVNPNSKIPALLDQS---GEKPIRVFESGSI 121
Cdd:PRK13972   2 IDLYFAPTPNGHKITLFLEE------AELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSpadGGEPLSLFESGAI 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270 122 LVYLAEKFGALLPNDLATRTETLNWLFWQMGSAPYVGGGFGHFYAYAPEKFEYPINRFTMETKRQLDVLNRQLAENRYLA 201
Cdd:PRK13972  76 LLYLAEKTGLFLSHETRERAATLQWLFWQVGGLGPMLGQNHHFNHAAPQTIPYAIERYQVETQRLYHVLNKRLENSPWLG 155

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 741126270 202 GDSYTIADIAVWPWYGGLVQnalysagEFLSVHEYEHVIRWADEIAARPA 251
Cdd:PRK13972 156 GENYSIADIACWPWVNAWTR-------QRIDLAMYPAVKNWHERIRSRPA 198

C-terminal, alpha helical domain of Escherichia coli YfcG Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YfcG-like subfamily; composed of the Escherichia coli YfcG and related 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. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. YfcG is one of nine GST homologs in Escherichia coli. It is expressed predominantly during the late stationary phase where the predominant form of GSH is glutathionylspermidine (GspSH), suggesting that YfcG might interact with GspSH. It has very low or no GSH transferase or peroxidase activity, but displays a unique disulfide bond reductase activity that is comparable to thioredoxins (TRXs) and glutaredoxins (GRXs). However, unlike TRXs and GRXs, YfcG does not contain a redox active cysteine residue and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YcfG reveals a bound GSSG molecule in its active site. The actual physiological substrates for YfcG are yet to be identified.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270 140 RTETLNWLFWQMGSAPYVGGGFGHFYAYAPEKFEYPINRFTMETKRQLDVLNRQLAENRYLAGDSYTIADIAVWPWyggl 219
Cdd:cd10291    2 RYAVLQWLMWQMGGLGPMQGQAHHFKRYAPEKIPYAIKRYTNETKRLYGVLDRRLAKSKYLAGDEYSIADIAIWPW---- 77

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 741126270 220 vqnALYSAGEFLSVHEYEHVIRWADEIAARPAVIRG 255
Cdd:cd10291   78 ---VARHEWQGIDLADFPNLKRWFERLAARPAVQKG 110

C-terminal, alpha helical domain of fungal Ure2p Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Ure2p subfamily; composed of the Saccharomyces cerevisiae Ure2p and related fungal proteins. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The N-terminal thioredoxin-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of 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 active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270 146 WLFWQM-GSAPYVGGgFGHFYAYAPEKFEYPINRFTMETKRQLDVLNRQLAE--NRYLAGDSYTIADIAVWPWYGGLvqN 222
Cdd:cd10293    8 WLFFQAsGQGPYWGQ-AGWFNVFHAEKVPSAIERYTNEIRRVLGVLETALAEryRVWLVGDKFTIADLAFVPWNNVV--D 84

                         90       100       110
                 ....*....|....*....|....*....|...
gi 741126270 223 ALYSAGEFLSVHEYEHVIRWADEIAARPAVIRG 255
Cdd:cd10293   85 MIFIDPELDIKKEFPHVYKWLKRMLARPAVKKA 117

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 741126270 187 LDVLNRQLAENRYLAGDSYTIADIAVwpwYGGLV--QNALYSAGEflsvhEYEHVIRWADEIAARPAV 252
Cdd:cd03182   57 LPVLDKRLAESPYVAGDRFSIADITA---FVALDfaKNLKLPVPE-----ELTALRRWYERMAARPSA 116

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270  65 LLALGHSGAEYDAWLIKIGDGDQFSSGFVDVNPNSKIPALLDQSgekpIRVFESGSILVYLAEKFGA----LLPNDLATR 140
Cdd:PLN02395  17 LVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGD----YKIFESRAIMRYYAEKYRSqgpdLLGKTIEER 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270 141 TETLNWLFWQMGS-APYVGGGFGHFyAYAPEKFEYPINRFTMETKRQ----LDVLNRQLAENRYLAGDSYTIADIAVWPW 215
Cdd:PLN02395  93 GQVEQWLDVEATSyHPPLLNLTLHI-LFASKMGFPADEKVIKESEEKlakvLDVYEARLSKSKYLAGDFVSLADLAHLPF 171

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 741126270 216 YGGLVQnalySAGEFLSVHEYEHVIRWADEIAARPA 251
Cdd:PLN02395 172 TEYLVG----PIGKAYLIKDRKHVSAWWDDISSRPA 203

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 741126270 146 WLFWQMGSAPYVGGGFGHFYAYAPEKFEYPINRFTMETKRQLDVLNRQLAENRYLAGDSYTIADIAVWPWygglVQNALY 225
Cdd:cd00299    4 LEDWADATLAPPLVRLLYLEKVPLPKDEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPV----LARLEA 79

                         90
                 ....*....|....*....
gi 741126270 226 SAGEFLSVHEYEHVIRWAD 244
Cdd:cd00299   80 LGPYYDLLDEYPRLKAWYD 98

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270  97 PNSKIPALLDQSgekpIRVFESGSILVYLAEKFG----ALLPNDLATRTETLNWL-----FWQMGSAPYVGGGFghFYAY 167
Cdd:PLN02473  50 PFGQVPAIEDGD----LKLFESRAIARYYATKYAdqgtDLLGKTLEHRAIVDQWVevennYFYAVALPLVINLV--FKPR 123

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270 168 APEKFEYP-INRFTMETKRQLDVLNRQLAENRYLAGDSYTIADIAVWPWYGGLVQNALYSAgeflSVHEYEHVIRWADEI 246
Cdd:PLN02473 124 LGEPCDVAlVEELKVKFDKVLDVYENRLATNRYLGGDEFTLADLTHMPGMRYIMNETSLSG----LVTSRENLNRWWNEI 199

                 ....*
gi 741126270 247 AARPA 251
Cdd:PLN02473 200 SARPA 204

C-terminal, alpha helical domain of an unknown subfamily 7 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 7; composed of uncharacterized 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 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270 171 KFEYPIN--RFTMETKRQLDVLNRQLAENRYLAGDSYTIADIAVWPWYgglvqnALYSAGEfLSVHEYEHVIRWADEIAA 248
Cdd:cd03206   24 LFGAPLDpeRARAISHRLLRLLDQHLAGRDWLAGDRPTIADVACYPYI------ALAPEGG-VSLEPYPAIRAWLARVEA 96

                 ..
gi 741126270 249 RP 250
Cdd:cd03206   97 LP 98

Glutathione S-transferase C-terminal-like, alpha helical domain of Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 3; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein (AIMP) 3 subfamily; AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex that functions as a molecular hub to coordinate protein synthesis. There are three AIMPs, named AIMP1-3, which play diverse regulatory roles. AIMP3, also called p18 or eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1), contains a C-terminal domain with similarity to the C-terminal alpha helical domain of GSTs. It specifically interacts with methionyl-tRNA synthetase (MetRS) and is translocated to the nucleus during DNA synthesis or in response to DNA damage and oncogenic stress. In the nucleus, it interacts with ATM and ATR, which are upstream kinase regulators of p53. It appears to work against DNA damage in cooperation with AIMP2, and similar to AIMP2, AIMP3 is also a haploinsufficient tumor suppressor. AIMP3 transgenic mice have shorter lifespans than wild-type mice and they show characteristics of progeria, suggesting that AIMP3 may also be involved in cellular and organismal aging.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 741126270 184 KRQLDVLNRQLAENRYLAGDSYTIADIAVwpWYGglvqnaLYSAGEFLSVHEYE---HVIRWADEIAARPAVIRGRKVN 259
Cdd:cd10305   28 KSLLKELNSYLQDRTYLVGHKLTLADVVL--YYG------LHPIMKDLSPQEKEqylNVSRWFDHVQHLPGIRQHLPLI 98

Glutathione S-transferase C-terminal-like, alpha helical domain of various Aminoacyl-tRNA synthetases and similar domains; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl-tRNA synthetase (AaRS)-like subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of some eukaryotic AaRSs, as well as similar domains found in proteins involved in protein synthesis including Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 2 (AIMP2), AIMP3, and eukaryotic translation Elongation Factor 1 beta (eEF1b). AaRSs comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. AaRSs in this subfamily include GluRS from lower eukaryotes, as well as GluProRS, MetRS, and CysRS from higher eukaryotes. AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex found in higher eukaryotes. The GST_C-like domain is involved in protein-protein interactions, mediating the formation of aaRS complexes such as the MetRS-Arc1p-GluRS ternary complex in lower eukaryotes and the multi-aaRS complex in higher eukaryotes, that act as molecular hubs for protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270 182 ETKRQLDVLNRQLAENRYLAGDSYTIADIAVWpwygglvqNALYSAGEFLSVHE---YEHVIRWADEIAA 248
Cdd:cd10289   20 ELEALLKSLNSYLASRTFLVGYSLTLADVAVF--------SALYPSGQKLSDKEkkkFPHVTRWFNHIQN 81

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 741126270  60 IMLEELlalghsGAEYDAWLIKIGDGDQFSSGFVDVNPNSKIPALLDQSGEkpiRVFESGSILVYLAEKF 129
Cdd:cd03057   16 IALEEL------GLPFELVRVDLRTKTQKGADYLAINPKGQVPALVLDDGE---VLTESAAILQYLADLH 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 741126270  70 HSGAEYDAWLIKIGDGDQFSSGFVDVNPNSKIPALLDQSgekpIRVFESGSILVYLAEKF 129
Cdd:cd03050   21 LNKIPFEECPIDLRKGEQLTPEFKKINPFGKVPAIVDGD----FTLAESVAILRYLARKF 76

Glutathione S-transferase C-terminal-like, alpha helical domain of the Gamma subunit of Elongation Factor 1B and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Gamma subunit of Elongation Factor 1B (EF1Bgamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds to membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression. Also included in this subfamily is the GST_C-like domain at the N-terminus of human valyl-tRNA synthetase (ValRS) and its homologs. Metazoan ValRS forms a stable complex with Elongation Factor-1H (EF-1H), and together, they catalyze consecutive steps in protein biosynthesis, tRNA aminoacylation and its transfer to EF.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270 144 LNWLFWQMGSAPYVgggfghfyAYAPEKFEypinrftMETKRQLDVLNRQLAENRYLAGDSYTIADIAVwpwyGGLVQNA 223
Cdd:cd03181   21 ATWVLPLLGIAPYN--------KKAVDKAK-------EDLKRALGVLEEHLLTRTYLVGERITLADIFV----ASALLRG 81

                         90       100       110
                 ....*....|....*....|....*....|.
gi 741126270 224 LYSA--GEFLSvhEYEHVIRWADEIAARPAV 252
Cdd:cd03181   82 FETVldPEFRK--KYPNVTRWFNTVVNQPKF 110

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 741126270   53 PNGVKVTIMLEELlalghsGAEYDAWLIKIgDGDQFSSGFVDVNPNSKIPALLDQSGEkpiRVFESGSILVYLAEK 128
Cdd:pfam13409   3 PFSHRVRLALEEK------GLPYEIELVDL-DPKDKPPELLALNPLGTVPVLVLPDGT---VLTDSLVILEYLEEL 68

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 741126270  45 LQLYSLA-TPNGVKVTIMLEeLLALGHSGAEYDawlikIGDGDQFSSGFVDVNPNSKIPALLDqsGEKPIRvfESGSILV 123
Cdd:cd03056    1 MKLYGFPlSGNCYKVRLLLA-LLGIPYEWVEVD-----ILKGETRTPEFLALNPNGEVPVLEL--DGRVLA--ESNAILV 70

                 ...
gi 741126270 124 YLA 126
Cdd:cd03056   71 YLA 73

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.

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gi 741126270  44 PLQLYSLA-TPNGVKVTIMLEEllalghSGAEYDAWLIKIGDGDQFSSGFVDVNPNSKIPALLDQsgekPIRVFESGSIL 122
Cdd:cd03053    1 VLKLYGAAmSTCVRRVLLCLEE------KGVDYELVPVDLTKGEHKSPEHLARNPFGQIPALEDG----DLKLFESRAIT 70

                 ....*.
gi 741126270 123 VYLAEK 128
Cdd:cd03053   71 RYLAEK 76

C-terminal, alpha helical domain of an unknown subfamily 8 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 8; composed of Agrobacterium tumefaciens GST and other 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 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 three-dimensional structure of Agrobacterium tumefaciens GST has been determined but there is no information on its functional characterization.

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gi 741126270 184 KRQLDVLNRQLAENRYLAGDSYTIADIavwpwyggLVQNALYSAGEFLSVHEYEHVIRWADEIAARPA 251
Cdd:cd03207   42 DERLAALEAALAGRPYLVGERFSAADL--------LLASVLRWARAFGLLPEYPALRAYVARCTARPA 101

Glutathione S-transferase C-terminal-like, alpha helical domain of Glutamyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, Glutamyl-tRNA synthetase (GluRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of GluRS from lower eukaryotes. Aminoacyl-tRNA synthetases (aaRSs) comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. The GST_C-like domain of GluRS is involved in protein-protein interactions. This domain mediates the formation of the MetRS-Arc1p-GluRS ternary complex found in lower eukaryotes, which is considered an evolutionary intermediate between prokaryotic aaRS and the multi-aaRS complex found in higher eukaryotes. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

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gi 741126270 187 LDVLNRQLAENRYLAGDSYTIADIAVWpwyGGLVQNALysAGEFLSVHEYEHVIRW 242
Cdd:cd10306   30 LEELDSHLTLRTFIVGYSLSLADIAVW---GALRGNGV--AGSLIKNKVYVNLSRW 80