stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191   2 MVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILVERDLILYESNIINEYIDERFPHPQLMP 81
Cdd:PRK09481  11 MTLFSGPTDIYSHQVRIVLAEKGVSVEIEQVEKDNLPQDLIDLNPYQSVPTLVDRELTLYESRIIMEYLDERFPHPPLMP 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191  82 ADPVQRARARLFLLNFEKELFVHVSTLENEKGKAAeknhEKARLAIRDRLTQLAPIFVKNKYMLGEEFSMLDVAIAPLLW 161
Cdd:PRK09481  91 VYPVARGESRLMMHRIEKDWYSLMNKIVNGSASEA----DAARKQLREELLAIAPVFGEKPYFMSEEFSLVDCYLAPLLW 166

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 493445191 162 RLDHYGIELSKNAAPLMK-YAERIFSRPAYIEALTPSEKVMR 202
Cdd:PRK09481 167 RLPVLGIELSGPGAKELKgYMTRVFERDSFLASLTEAEREMR 208

stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191   2 MVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILVERDLILYESNIINEYIDERFPHPQLMP 81
Cdd:PRK09481  11 MTLFSGPTDIYSHQVRIVLAEKGVSVEIEQVEKDNLPQDLIDLNPYQSVPTLVDRELTLYESRIIMEYLDERFPHPPLMP 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191  82 ADPVQRARARLFLLNFEKELFVHVSTLENEKGKAAeknhEKARLAIRDRLTQLAPIFVKNKYMLGEEFSMLDVAIAPLLW 161
Cdd:PRK09481  91 VYPVARGESRLMMHRIEKDWYSLMNKIVNGSASEA----DAARKQLREELLAIAPVFGEKPYFMSEEFSLVDCYLAPLLW 166

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 493445191 162 RLDHYGIELSKNAAPLMK-YAERIFSRPAYIEALTPSEKVMR 202
Cdd:PRK09481 167 RLPVLGIELSGPGAKELKgYMTRVFERDSFLASLTEAEREMR 208

GST_N 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 TRX-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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 493445191   2 MVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILVERDLILYESNIINEYIDERF 74
Cdd:cd03059    1 MTLYSGPDDVYSHRVRIVLAEKGVSVEIIDVDPDNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDERF 73

intracellular chloride channel protein; The Organellar Chloride Channel (O-ClC) Family (TC 1.A.12) Proteins of the O-ClC family are voltage-sensitive chloride channels found in intracellular membranes but not the plasma membranes of animal cells. They are found in human nuclear membranes, and the bovine protein targets to the microsomes, but not the plasma membrane, when expressed in Xenopus laevis oocytes. These proteins are thought to function in the regulation of the membrane potential and in transepithelial ion absorption and secretion in the kidney. [Transport and binding proteins, Anions]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191   10 CPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILVERDLILYESNIINEYIDERFPHPQLMPADPVQRAR 89
Cdd:TIGR00862  19 CPFSQRLFMILWLKGVVFNVTTVDLKRKPEDLQNLAPGTHPPFLTYNTEVKTDVNKIEEFLEETLCPPRYPKLSPKHPES 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191   90 ARLFLlnfekELFVHVSTLENEKGKAAEKNHEKARLAIRDRL---------------TQLAPIFVKNKYMLGEEFSMLDV 154
Cdd:TIGR00862  99 NTAGL-----DIFAKFSAYIKNSNPEANDNLEKGLLKALKKLddylnsplpeeidedSAEDEKVSRRKFLDGDELTLADC 173

                  ....*.
gi 493445191  155 AIAPLL 160
Cdd:TIGR00862 174 NLLPKL 179

stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191   2 MVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILVERDLILYESNIINEYIDERFPHPQLMP 81
Cdd:PRK09481  11 MTLFSGPTDIYSHQVRIVLAEKGVSVEIEQVEKDNLPQDLIDLNPYQSVPTLVDRELTLYESRIIMEYLDERFPHPPLMP 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191  82 ADPVQRARARLFLLNFEKELFVHVSTLENEKGKAAeknhEKARLAIRDRLTQLAPIFVKNKYMLGEEFSMLDVAIAPLLW 161
Cdd:PRK09481  91 VYPVARGESRLMMHRIEKDWYSLMNKIVNGSASEA----DAARKQLREELLAIAPVFGEKPYFMSEEFSLVDCYLAPLLW 166

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 493445191 162 RLDHYGIELSKNAAPLMK-YAERIFSRPAYIEALTPSEKVMR 202
Cdd:PRK09481 167 RLPVLGIELSGPGAKELKgYMTRVFERDSFLASLTEAEREMR 208

GST_N 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 TRX-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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 493445191   2 MVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILVERDLILYESNIINEYIDERF 74
Cdd:cd03059    1 MTLYSGPDDVYSHRVRIVLAEKGVSVEIIDVDPDNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDERF 73

Glutathione S-transferase (GST) family, N-terminal 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 subfamily, a member of the DsbA family). 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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, metaxin 2 and stringent starvation protein A.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 493445191   2 MVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLFNKP-EDISVMNPYGQVPILVERDLILYESNIINEYID 71
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEqEEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191   1 MMVLYSGT--TCPFSQRCRLVLFEKGMDFEIRDVDLFNKPEdisVMNPYGQ------VPILVERDLILYESNIINEYIDE 72
Cdd:PRK15113   5 AITLYSDAhfFSPYVMSAFVALQEKGLPFELKTVDLDAGEH---LQPTYQGysltrrVPTLQHDDFELSESSAIAEYLEE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191  73 RFP---HPQLMPADPVQRARARLF-------LLNFEKE-----LFV-HVSTLENEKGKAAeknheKARL-AIRDRLtqLA 135
Cdd:PRK15113  82 RFAppaWERIYPADLQARARARQIqawlrsdLMPLREErptdvVFAgAKKAPLSEAGKAA-----AEKLfAVAERL--LA 154

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 493445191 136 PifvkNKYMLGEEFSMLDVAIAPLLWRLDHYGIELSknaAPLMKYAERIFSRPA 189
Cdd:PRK15113 155 P----GQPNLFGEWCIADTDLALMLNRLVLHGDEVP---ERLADYATFQWQRAS 201

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 493445191   2 MVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLF---NKPEDISVMNPYGQVPILVERDLILYESNIINEYIDER 73
Cdd:cd03053    2 LKLYGAAMSTCVRRVLLCLEEKGVDYELVPVDLTkgeHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

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 493445191    2 MVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDL---FNKPEDISVMNPYGQVPILVERDLILYESNIINEYIDE 72
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFgagPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

GST_N family, Class Tau 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 plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 493445191   2 MVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNP-YGQVPILVERDLILYESNIINEYIDERF 74
Cdd:cd03058    1 VKLLGAWASPFVLRVRIALALKGVPYEYVEEDLGNKSELLLASNPvHKKIPVLLHNGKPICESLIIVEYIDEAW 74

glutathione S-transferase DHAR1

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191  10 CPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILVERDLILYESNIINEYIDERFPHPQLMPADPVQRAR 89
Cdd:PLN02378  20 CPFSQRALLTLEEKSLTYKIHLINLSDKPQWFLDISPQGKVPVLKIDDKWVTDSDVIVGILEEKYPDPPLKTPAEFASVG 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191  90 ARLF--LLNF----------EKELFVHVSTLENEKgkaaeKNHEkarlairdrltqlapifvkNKYMLGEEFSMLDVAIA 157
Cdd:PLN02378 100 SNIFgtFGTFlkskdsndgsEHALLVELEALENHL-----KSHD-------------------GPFIAGERVSAVDLSLA 155

                 ....*.
gi 493445191 158 PLLWRL 163
Cdd:PLN02378 156 PKLYHL 161

GST_N family, Omega-like subfamily; composed of uncharacterized proteins with similarity to class Omega 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. 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. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. Like Omega enzymes, proteins in this subfamily contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 493445191   3 VLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILV-ERDLILYES 63
Cdd:cd03060    2 ILYSFRRCPYAMRARMALLLAGITVELREVELKNKPAEMLAASPKGTVPVLVlGNGTVIEES 63

GST_N family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 493445191   2 MVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLF---NKPEDISVMNPYGQVPILVERD-LILYESNIINEYID 71
Cdd:cd03051    1 MKLYDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAageQRSPEFLAKNPAGTVPVLELDDgTVITESVAICRYLE 74

GST_N family, Chloride Intracellular Channel (CLIC) subfamily; composed of CLIC1-5, p64, parchorin and similar proteins. They are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division and apoptosis. They can exist in both water-soluble and membrane-bound states, and are found in various vesicles and membranes. Biochemical studies of the C. elegans homolog, EXC-4, show that the membrane localization domain is present in the N-terminal part of the protein. The structure of soluble human CLIC1 reveals that it is monomeric and it adopts a fold similar to GSTs, containing an N-terminal domain with a TRX fold and a C-terminal alpha helical domain. Upon oxidation, the N-terminal domain of CLIC1 undergoes a structural change to form a non-covalent dimer stabilized by the formation of an intramolecular disulfide bond between two cysteines that are far apart in the reduced form. The CLIC1 dimer bears no similarity to GST dimers. The redox-controlled structural rearrangement exposes a large hydrophobic surface, which is masked by dimerization in vitro. In vivo, this surface may represent the docking interface of CLIC1 in its membrane-bound state. The two cysteines in CLIC1 that form the disulfide bond in oxidizing conditions are essential for dimerization and chloride channel activity, however, in other subfamily members, the second cysteine is not conserved.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 493445191  10 CPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILVERDLILYESNIINEYIDE 72
Cdd:cd03061   22 CPFCQRLFMVLWLKGVVFNVTTVDMKRKPEDLKDLAPGTQPPFLLYNGEVKTDNNKIEEFLEE 84

intracellular chloride channel protein; The Organellar Chloride Channel (O-ClC) Family (TC 1.A.12) Proteins of the O-ClC family are voltage-sensitive chloride channels found in intracellular membranes but not the plasma membranes of animal cells. They are found in human nuclear membranes, and the bovine protein targets to the microsomes, but not the plasma membrane, when expressed in Xenopus laevis oocytes. These proteins are thought to function in the regulation of the membrane potential and in transepithelial ion absorption and secretion in the kidney. [Transport and binding proteins, Anions]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191   10 CPFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILVERDLILYESNIINEYIDERFPHPQLMPADPVQRAR 89
Cdd:TIGR00862  19 CPFSQRLFMILWLKGVVFNVTTVDLKRKPEDLQNLAPGTHPPFLTYNTEVKTDVNKIEEFLEETLCPPRYPKLSPKHPES 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493445191   90 ARLFLlnfekELFVHVSTLENEKGKAAEKNHEKARLAIRDRL---------------TQLAPIFVKNKYMLGEEFSMLDV 154
Cdd:TIGR00862  99 NTAGL-----DIFAKFSAYIKNSNPEANDNLEKGLLKALKKLddylnsplpeeidedSAEDEKVSRRKFLDGDELTLADC 173

                  ....*.
gi 493445191  155 AIAPLL 160
Cdd:TIGR00862 174 NLLPKL 179

glutathione S-transferase

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 493445191   1 MMV-LYSGTTCPFSQRCRLVLFEKGMDFEIRDVDL----FNKPEDIsVMNPYGQVPILVERDLILYESNIINEYIDERF 74
Cdd:PLN02473   1 MVVkVYGQIKAANPQRVLLCFLEKGIEFEVIHVDLdkleQKKPEHL-LRQPFGQVPAIEDGDLKLFESRAIARYYATKY 78

glutathione S-transferase

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 493445191   1 MMVLYSGTTCPFSQRCRLVLFEKGMDFEIRDVDLF---NKPEDISVMNPYGQVPILVERDLILYESNIINEYIDERF 74
Cdd:PLN02395   1 MVLKVYGPAFASPKRALVTLIEKGVEFETVPVDLMkgeHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKY 77

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 493445191 104 HVSTLENEKGKAAEKNH--EKARL-AIRDRltQLApifvKNKYMLGEEFSMLDVAIAPLLWRLDHYGIELsKNAAPLMKY 180
Cdd:cd10291   25 HFKRYAPEKIPYAIKRYtnETKRLyGVLDR--RLA----KSKYLAGDEYSIADIAIWPWVARHEWQGIDL-ADFPNLKRW 97

                         90
                 ....*....|...
gi 493445191 181 AERIFSRPAYIEA 193
Cdd:cd10291   98 FERLAARPAVQKG 110

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        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 493445191  22 EKGMDFEIRDVDL---FNKPEDISVMNPYGQVPILVERDLILYESNIINEYI 70
Cdd:cd03047   21 ELGLPYERIDAGGqfgGLDTPEFLAMNPNGRVPVLEDGDFVLWESNAILRYL 72

Thioredoxin (TRX) superfamily; a large, diverse group of proteins containing a TRX-fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include TRX, protein disulfide isomerase (PDI), tlpA-like, glutaredoxin, NrdH redoxin, and the bacterial Dsb (DsbA, DsbC, DsbG, DsbE, DsbDgamma) protein families. Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins and glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 493445191   2 MVLYSGTTCPFSQRCRLVLFE-----KGMDFEIRDVDLFNKPEDISVMNPYGQVPILV 54
Cdd:cd01659    1 LVLFYAPWCPFCQALRPVLAElallnKGVKFEAVDVDEDPALEKELKRYGVGGVPTLV 58

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 493445191  11 PFSQRCRLV---LFEKGMDFEIRDVDLFNK----PEDISVmNPYGQVPILVERDLILYESNIINEYIDERF 74
Cdd:cd03050    7 LMSQPSRAVyifLKLNKIPFEECPIDLRKGeqltPEFKKI-NPFGKVPAIVDGDFTLAESVAILRYLARKF 76

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 493445191  86 QRARARLFLLNFEKELFVHVSTLENEKGKAAEKnHEKARLAIRDRLTQLAPIFVKNKYMLGEEFSMLDVAIAPLLWRLDH 165
Cdd:cd00299    1 VRALEDWADATLAPPLVRLLYLEKVPLPKDEAA-VEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEA 79

                         90       100
                 ....*....|....*....|.
gi 493445191 166 YGIELSKNAAP--LMKYAERI 184
Cdd:cd00299   80 LGPYYDLLDEYprLKAWYDRL 100

Glutaredoxin (GRX) family; composed of GRX, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, as well as E. coli GRX1 and GRX3, which are members of this family. E. coli GRX2, however, is a 24-kDa protein that belongs to the GSH S-transferase (GST) family.

                         10        20        30
                 ....*....|....*....|....*....|.
gi 493445191   3 VLYSGTTCPFSQRCRLVLFEKGMDFEIRDVD 33
Cdd:cd02066    3 VVFSKSTCPYCKRAKRLLESLGIEFEEIDIL 33

GST_N family, Gamma subunit of Elongation Factor 1B (EFB1gamma) 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 TRX-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 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 493445191  24 GMDFEIRDVDLF--NKPEDISVMNPYGQVPILV-ERDLILYESNIINEYI 70
Cdd:cd03044   23 GLDVEIVDFQPGkeNKTPEFLKKFPLGKVPAFEgADGFCLFESNAIAYYV 72

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 493445191  87 RARARLF-LLNF-----EKELFVHVSTLENEKGKAAEKNHEKARLAIRDRLTQLAPIFVKNKYMLGEEFSMLDVAIAPLL 160
Cdd:cd03188    1 LERARLLeWLNFiaselHKAFGPLFYPARWADDALAEEVKAAARERLERRLAYLDAQLAGGPYLLGDQFSVADAYLFVVL 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 493445191 161 -WrLDHYGIELSKNAApLMKYAERIFSRPAYIEAL 194
Cdd:cd03188   81 rW-ARAVGLDLSDWPH-LAAYLARVAARPAVQAAL 113

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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 tumours.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 493445191  17 RLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQVPILVERDLILYESNII 66
Cdd:cd03076   17 RLLLADQGISWEEERVTYEEWQESLKPKMLFGQLPCFKDGDLTLVQSNAI 66

GST_N family, Beta etherase LigE subfamily; composed of proteins similar to Sphingomonas paucimobilis beta etherase, LigE, a GST-like protein that catalyzes the cleavage of the beta-aryl ether linkages present in low-moleculer weight lignins using GSH as the hydrogen donor. This reaction is an essential step in the degradation of lignin, a complex phenolic polymer that is the most abundant aromatic material in the biosphere. The beta etherase activity of LigE is enantioselective and it complements the activity of the other GST family beta etherase, LigF.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 493445191  11 PFSQRCRLVLFEKGMDFEIRDVDLFNKPEDISVMNPYGQ--VPILVERD-LILYESNIINEYIDERFP 75
Cdd:cd03038   17 PNVWKTRLALNHKGLEYKTVPVEFPDIPPILGELTSGGFytVPVIVDGSgEVIGDSFAIAEYLEEAYP 84