Glutathione S-transferase

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{{STRUCTURE_1pkw| size='400' side='right' caption='Human glutathione S-transferase class α complex with glutathione (PDB entry [[1pkw]])' scene=''}}
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<StructureSection load='1fhe' size='350' side='right' caption='Glutathione S-tansferase complex with glutathione (PDB entry [[1fhe]])' scene='52/524296/Cv/1'>
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== Function ==
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'''Glutathione S-transferase''' (GST) catalyzes the conjugation of reduced glutathione (GSH) to a variety of exogenous and endogenous hydrophobic electrophiles. For example, GST can detoxify peroxidised lipids. All eukaryotes possess a variety of GSTs with catalytic and non-catalytic activities. GST is divided into classes: α, δ, ε, κ, μ, ν, ω, π, ρ, σ (hematopoietic prostaglandin D synthase), τ, χ, ϑ, ζ and microsomal<ref>PMID:21428697</ref>.
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*'''epsilon glutathione S-transferase''' has a role in insecticide resistance<ref>PMID:26487708</ref>.
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*'''kappa glutathione S-transferase''' is found in mitochondria and peroxisomes. It may be involved in lipid metabolism<ref>PMID:21428694</ref>.
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*'''mu glutathione S-transferase''' detoxify carcinogens in tobacco smoke<ref>PMID:8485718</ref>.
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*'''nu glutathione S-transferase''' breaks the beta-aryl ether bond of lignin<ref>PMID:29449375</ref>.
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*'''pi glutathione S-transferase''' has a role in carcinogenic processes<ref>PMID:9679544</ref>.
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*'''rho glutathione S-transferase''' detoxifies water from the pollutant dichloroacetate<ref>PMID:25685659</ref>.
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*'''sigma glutathione S-transferase''' is a detoxifying agent providing drug resistance and acting as vaccine antigen<ref>PMID:38668546</ref>.
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*'''omega glutathione S-transferase''' catalyzes a range of thiol transferase reactions like biotransformation of haloketones to nontoxic acetophenones<ref>PMID:21495794</ref>.
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*'''zeta glutathione S-transferase''' catalyzes the reaction of glutathione with Endo- and xenobiotics<ref>PMID:21303221</ref>.
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*'''tau glutathione S-transferase''' and '''LanCL1 glutathione S-transferase''' are involved in oxidative stress response<ref>PMID:15037622</ref>.
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*'''phi glutathione S-transferase''' is plant-specific<ref>PMID:26884677</ref>.
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*'''microsomali glutathione S-transferase''' protects cells from cytostatic drugs and from oxidative stress<ref>PMID:21495795</ref>.
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==Relevance==
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GST are targets for anti-diabetic drugs.
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== Structural highlights ==
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'''Glutathione S-transferase''' (GST) catalyzes the conjugation of reduced glutathione (GSH) to a variety of exogenous and endogenous hydrophobic electrophiles. For example, GST can detoxify peroxidised lipids. All eukaryotes possess a variety of GSTs with catalytic and non-catalytic activities. GST is divided into classes: α, δ, ε, κ, μ, ν, ω, π, ρ, σ (hematopoietic prostaglandin D synthase), τ, χ, ϑ, ζ and microsomal.
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The <scene name='52/524296/Cv/4'>glutathione binding site is at the N-terminal of GST</scene><ref>PMID:9367777</ref>.
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===GST===
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==3D structures of glutathione S-transferase==
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[[Glutathione S-transferase 3D structures]]
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[[4hz4]] – GST – ''Actinobacillus pleuropneumoniae''''Italic text''<br />
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</StructureSection>
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[[1gsb]], [[1gsc]] – rGST – rat<br />
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[[3ubk]] – LiGST – Leptospira interrogans<br />
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[[3uap]] - GST – Methylococcus capsulatus<br />
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[[1aw9]] - cGST III – corn<br />
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[[1okt]] – PfGST – Plasmodium falciparum<br />
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[[3fr6]] - PfGST (mutant) <br />
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[[1tw9]] – GST - Heligmosomoides polygyrus<br />
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[[1yq1]] - CeGST – Caenorhabditis elegans<br />
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[[1y6e]] - SjGST – Schistosoma japonicum<br />
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[[2fno]], [[3lq7]] - AtGST – Agrobacterium tumefaciens<br />
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[[2on7]] – NaGST-1 – Necator americanus<br />
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[[3erf]] - yGST II – yeast<br />
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[[3f6f]] – DmGST – Drosophila melanogaster<br />
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[[3lxt]] - PsfGST – Pseudomonas fluorescens<br />
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[[4eci]] - PaGST – Pseudomonas aeruginosa<br />
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[[3niv]] - GST – Legionella pneumophila<br />
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[[3tot]] - RsGST – Ralstonia solanacearum<br />
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[[3ay8]] - siGST – silkworm<br />
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[[3uap]] - McGST – Methylococcus capsulatus
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===GST binary complex with GSH===
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== References ==
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<references/>
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[[2x64]] – GST + GSH – Xylella fastidiosa<br />
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[[Category:Topic Page]]
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[[4hz2]] - GST + GSH - Xanthobacter autotrophicus<br />
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[[4ecj]] - PaGST + GSH<BR />
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[[1fhe]], [[2fhe]] - GST + GSH – Fasciola hepatica<br />
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[[1pmt]], [[2pmt]] - GST + GSH – Proteus mirabilis<br />
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[[1m0u]], [[3gh6]] - DmGST + GSH<BR />
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[[1oe7]], [[1oe8]] - ShGST + GSH – Schistosoma haematobium<br />
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[[1u3i]] - GST + GSH - Schistosoma mansoni<br />
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[[1oyj]] - GST + GSH - rice<br />
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[[1u87]] - SjGST + GSH<BR />
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[[2dsa]], [[2gdr]] - GST + GSH – Burkholderia xenovorans<br />
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[[2on5]] – NaGST-2 + GSH<BR />
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[[2nto]] - OaGST + GSH – Ochrobactrum anthropi<br />
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[[2pvq]] - OaGST (mutant) + GSH<BR />
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[[3ibh]] - yGST II + GSH<BR />
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[[3fr9]] - PfGST + GSH<BR />
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[[3m3m]] - PsfGST + GSH<BR />
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[[3lsz]] - GST + GSH – Rhodobacter sphaeroides<br />
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[[3n5o]] - GST + GSH – Coccidioides immitis<br />
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[[3tou]] - RsGST + GSH<BR />
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[[3uar]] - McGST + GSH<BR />
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[[4g9h]], [[4gci]] - GST + GSH – Yersinia pestis<br />
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[[4gf0]] - GST + GSH - Sulfitobacter
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===GST binary complex===
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[[3ubl]] - LiGST + GSH derivative<br />
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[[2gsq]] – GST + GSH derivative – squid<br />
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[[2gst]], [[3gst]], [[4gst]], [[5gst]], [[1gss]] - rGST + GSH derivative<br />
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[[1gnw]] - AtGST + GSH derivative – Arabidopsis thaliana <br />
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[[1aqv]] - hGST + GSH derivative – human<br />
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[[1gtb]], [[1gta]] - SjGST + praziquantel<br />
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[[1m99]], [[1m9a]], [[1m9b]] - SjGST + GSH derivative<br />
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[[1q4j]], [[2aaw]], [[3frc]] - PfGST + GSH derivative<br />
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[[3fr3]] - PfGST (mutant) + GSH derivative<br />
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[[1bx9]] - AtGST + herbicide<br />
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[[1bye]] - cGST I + herbicide <br />
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[[1axd]] – cGST I + lactoyl-GSH<BR />
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[[1a0f]], [[1n2a]] - GST + GSH derivative – Eschericia coli<br />
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[[1f2e]] - GST + GSH derivative<br /> – Sphingomonas paucimobilis<br />
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[[1mtc]] - rGST + GSH derivative<br />
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[[1ua5]] - SjGST + GSH derivative<br />
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[[1u88]] - SjGST (mutant) + GSH derivative<br />
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[[3erg]] - yGST II + GSH derivative<br />
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[[3qmz]] - yGST + dynein heavy chain<br />
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[[2ycd]] - AtGST + GSH derivative<br />
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===GST α class===
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[[1guh]], [[1gsd]], [[1k3o]], [[1pkz]] – hGST A1-1<br />
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[[1xwg]], [[3q74]], [[3u6v]] - hGST A1-1 (mutant) <br />
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[[1gum]] - hGST A4-4<br />
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[[1guk]] - mGST A4-4 – mouse<br />
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[[1vf4]] - GgGST A1-1 - chicken
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===GST α class complex with GSH===
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[[1pkw]] - hGST + GSH<BR />
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[[1usb]] - hGST (mutant) + GSH<BR />
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[[1f3a]] - mGST A1-1+ GSH<BR />
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[[3i69]], [[3i6a]] - hGST A1-1 (mutant)+ GSH<BR />
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[[2wju]] - hGST A2-2 + GSH<BR />
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[[4acs]] - hGST A2-2 (mutant) + GSH<BR />
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[[1tdi]] - hGST A3-3 + GSH<BR />
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[[1vf1]] - GgGST A1-1 + GSH<BR />
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===GST α class complex===
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[[1gsf]] – hGST A1-1 + ethacrynic acid<br />
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[[1ags]], [[1pl2]], [[1ydk]], [[2r3x]], [[2r6k]], [[3ktl]], [[3l0h]] – hGST (mutant) + GSH derivative<br />
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[[1k3l]], [[1k3y]], [[1pl1]] - hGST + GSH derivative<br />
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[[1gse]] – hGST (mutant) + GSH + ethacrynic acid<br />
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[[3ik9]] - hGST A1-1 + GSDN<br />
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[[2vct]] - hGST A2-2 + steroid<br />
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[[2vcv]] - hGST A3-3 + steroid<br />
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[[1gul]] - hGST A4-4+ iodobenzyl-GSH<BR />
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[[3ik7]] - hGST A4-4 + GSDHN <br />
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[[1b48]] - mGST A4-4 + GSH derivative<br />
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[[1f3b]] - mGST A1-1 + GSH derivative<br />
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[[1ml6]] - mGST A2-2+ GSH derivative<br />
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[[1ev4]], [[1ev9]] - rGST A1-1 (mutant) + GSH derivative<br />
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[[1vf2]], [[1vf3]] – GgGST A1-1 + GSH derivative<br />
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===GST δ class===
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[[1r5a]], [[1v2a]], [[1pn9]] - GST + GSH derivative - Anopheles cracens<br />
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[[3ein]] - DmGST + GSH<BR />
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[[3vk9]] - siGST
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===GST ε class===
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[[2il3]] - AgGST – Anopheles gambiae<br />
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[[2imi]] - AgGST + GSH<BR />
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[[2imk]] - AgGST + GSH derivative<br />
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===GST κ class===
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[[3rpp]] - hGST <br />
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[[1r4w]] - rGST + GSH derivative<br />
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[[1yzx]], [[3rpn]] - hGST + GSH derivative<br />
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===GST μ class===
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[[1gsb]], [[1gsc]] – rGST<br />
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[[6gsu]], [[6gsv]], [[6gsw]], [[6gsx]], [[6gsy]], [[5fwg]], [[3fyg]] - rGST (mutant) <br />
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[[1gtu]], [[2gtu]], [[3gtu]], [[4gtu]] - hGST<br />
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[[2dc5]] - mGST <br />
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[[2wrt]] - GST – Fasciola hepatica
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===GST μ class complex with GSH===
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[[1xw5]], [[1xw6]] - hGST + GSH<BR />
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[[2f8f]] - mGST (mutant) + GSH<BR />
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[[3crt]] - SjGST + GSH<BR />
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[[3cru]], [[3d0z]] - SjGST (mutant) + GSH<BR />
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===GST μ class complex===
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[[1gst]] - GgGST + GSH derivative<br />
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[[1c72]] - GgGST + conjugate<br />
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[[1hna]], [[1hnb]], [[1hnc]], [[1xwk]], [[1ykc]], [[1yj6]], [[2ab6]], [[2f3m]] – hGST + GSH derivative<br />
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[[2c4j]] - hGST (mutant) + GSH derivative<br />
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[[1b4p]] - rGST + GSH derivative<br />
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[[3gur]] - hGST + GSH + drug<br />
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[[3gus]] - hGST + drug
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===GST ν class===
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[[2ws2]] - GST – Haemonchus contortus
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===GST π class===
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[[1bay]] - mGST <br />
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[[10gs]], [[14gs]], [[16gs]], [[1lbk]] - hGST<br />
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[[22gs]], [[1eog]], [[1eoh]], [[3hjm]], [[3hkr]], [[3kmn]] - hGST (mutant)
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===GST π class complex with GSH===
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[[1gsy]] - mGST + GSH<BR />
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[[1tu7]], [[2hnl]] - OvGST + GSH - Onchocerca volvulus<br />
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[[5gss]], [[6gss]], [[7gss]], [[8gss]], [[19gs]], [[3dd3]] - hGST + GSH<BR />
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[[1md3]], [[1md4]], [[1px6]], [[1px7]], [[1kbn]] - hGST (mutant) + GSH<BR />
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[[3t2u]] - GST + GSH – Wuchereria bancrofti
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===GST π class complex===
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[[1gss]] – rGST + GSH derivative<br />
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[[1tu8]] - OvGST + GSH derivative<br />
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[[1glq]], [[1glp]], [[2glr]], [[1gti]] - mGST + GSH derivative<br />
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[[2oac]], [[2oad]], [[2oa7]], [[3o76]] - mGST (mutant) + GSH derivative<br />
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[[2gss]], [[3dgq]] – hGST + ethacrynic acid<br />
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[[3n9j]] - hGST + ethacrynic acid derivative<br />
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[[3gss]], [[11gs]] – hGST + ethacrynic acid + GSH<BR />
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[[3hjo]], [[3km6]], [[3kmo]] - hGST (mutant) + ethacrynic acid + GSH<BR />
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[[1pgt]], [[2pgt]], [[4gss]], [[17gs]], [[2j9h]], [[3csi]] - hGST (mutant) + GSH derivative<br />
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[[1aqw]], [[1aqx]], [[9gss]], [[12gs]], [[18gs]], [[3pgt]], [[4pgt]], [[1zgn]], [[2a2r]], [[2a2s]], [[3csh]] - hGST + GSH derivative<br />
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[[20gs]] - hGST + cibacron blue<br />
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[[13gs]], [[3csj]] - hGST + drug<br />
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[[3ie3]] - hGST (mutant) + drug
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===GST ρ class===
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[[3qav]] - AcGST – Atlantic clam<br />
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[[3qaw]] - AcGST + GSH<BR />
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===GST σ class===
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[[2c8u]], [[2cai]] - ShGST (mutant) <br />
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[[2ca8]] - ShGST + GSH<BR />
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[[1zl9]] - CeGST + GSH<BR />
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[[4ec0]], [[4edz]], [[4ee0]], [[4edy]], [[1iyh]], [[1iyi]], [[2vcq]], [[2vcw]], [[2vcx]], [[2vcz]], [[2vd0]], [[2vd1]] - hGST + GSH<BR />
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[[3vi7]] - hGST (mutant) + GSH<BR />
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[[1v40]], [[2cvd]], [[3ee2]], [[3kxo]] - hGST + GSH + inhibitor<br />
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[[3vi5]], [[3vi7]] - hGST (mutant) + GSH + inhibitor<br />
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[[2caq]] - ShGST (mutant) + GSH<BR />
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[[1pd2]] - rGST + GSH<BR />
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[[2c80]] - ShGST + GSH derivative<br />
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===GST ϑ class===
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[[2ljr]], [[2c3n]] - hGST <br />
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[[2c3t]] - hGST (mutant) <br />
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[[1ljr]] - hGST + GSH<BR />
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[[3mak]] - DmGST + GSH<BR />
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[[3ljr]] - hGST + GSH derivative<br />
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[[2c3q]] - hGST (mutant) + GSH derivative<br />
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===GST χ class===
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[[3ppu]] - GST + GSH – Phanerochaete chrysosporium
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===GST ω class===
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[[1eem]] – hGST<br />
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[[3q18]], [[3vln]] - hGST (mutant) <br />
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[[3rbt]] - siGST <br />
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[[3lfl]] - hGST + GSH<BR />
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[[3qag]], [[3q19]] - hGST (mutant) + GSH<BR />
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===GST ζ class===
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[[1e6b]] – AtGST<br />
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[[2cz3]] - mGST <br />
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[[2cz2]] - mGST + GSH<BR />
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===GST τ class===
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[[1gwc]] - GST – wheat<br />
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[[2vo4]] - sGST + GSH derivative – soybean<br />
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[[3fhs]] - sGST + GSH<BR />
+
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+
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===Microsomal GST===
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+
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[[2h8a]] - rGST + GSH<BR />
+

Current revision

Glutathione S-tansferase complex with glutathione (PDB entry 1fhe)

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References

  1. ↑ Oakley A. Glutathione transferases: a structural perspective. Drug Metab Rev. 2011 May;43(2):138-51. doi: 10.3109/03602532.2011.558093. Epub, 2011 Mar 23. PMID:21428697 doi:http://dx.doi.org/10.3109/03602532.2011.558093
  2. ↑ Wongsantichon J, Robinson RC, Ketterman AJ. Epsilon glutathione transferases possess a unique class-conserved subunit interface motif that directly interacts with glutathione in the active site. Biosci Rep. 2015 Oct 20;35(6). pii: e00272. doi: 10.1042/BSR20150183. PMID:26487708 doi:http://dx.doi.org/10.1042/BSR20150183
  3. ↑ Morel F, Aninat C. The glutathione transferase kappa family. Drug Metab Rev. 2011 May;43(2):281-91. PMID:21428694 doi:10.3109/03602532.2011.556122
  4. ↑ Nazar-Stewart V, Motulsky AG, Eaton DL, White E, Hornung SK, Leng ZT, Stapleton P, Weiss NS. The glutathione S-transferase mu polymorphism as a marker for susceptibility to lung carcinoma. Cancer Res. 1993 May 15;53(10 Suppl):2313-8 PMID:8485718
  5. ↑ Kontur WS, Bingman CA, Olmsted CN, Wassarman DR, Ulbrich A, Gall DL, Smith RW, Yusko LM, Fox BG, Noguera DR, Coon JJ, Donohue TJ. Novosphingobium aromaticivorans uses a Nu-class glutathione-S-transferase as a glutathione lyase in breaking the beta-aryl ether bond of lignin. J Biol Chem. 2018 Feb 15. pii: RA117.001268. doi: 10.1074/jbc.RA117.001268. PMID:29449375 doi:http://dx.doi.org/10.1074/jbc.RA117.001268
  6. ↑ Henderson CJ, McLaren AW, Moffat GJ, Bacon EJ, Wolf CR. Pi-class glutathione S-transferase: regulation and function. Chem Biol Interact. 1998 Apr 24;111-112:69-82. PMID:9679544 doi:10.1016/s0009-2797(97)00176-2
  7. ↑ Pandey T, Chhetri G, Chinta R, Kumar B, Singh DB, Tripathi T, Singh AK. Functional classification and biochemical characterization of a novel rho class glutathione S-transferase in Synechocystis PCC 6803. FEBS Open Bio. 2014 Nov 24;5:1-7. PMID:25685659 doi:10.1016/j.fob.2014.11.006
  8. ↑ Sánchez Pérez LC, Zubillaga RA, García-Gutiérrez P, Landa A. Sigma-Class Glutathione Transferases (GSTσ): A New Target with Potential for Helminth Control. Trop Med Infect Dis. 2024 Apr 16;9(4):85. PMID:38668546 doi:10.3390/tropicalmed9040085
  9. ↑ Board PG. The omega-class glutathione transferases: structure, function, and genetics. Drug Metab Rev. 2011 May;43(2):226-35. PMID:21495794 doi:10.3109/03602532.2011.561353
  10. ↑ Board PG, Anders MW. Glutathione transferase zeta: discovery, polymorphic variants, catalysis, Drug Metab Rev. 2011 May;43(2):215-25. PMID:21303221 doi:10.3109/03602532.2010.549132
  11. ↑ Kilili KG, Atanassova N, Vardanyan A, Clatot N, Al-Sabarna K, Kanellopoulos PN, Makris AM, Kampranis SC. Differential roles of tau class glutathione S-transferases in oxidative stress. J Biol Chem. 2004 Jun 4;279(23):24540-51. PMID:15037622 doi:10.1074/jbc.M309882200
  12. ↑ Munyampundu JP, Xu YP, Cai XZ. Phi Class of Glutathione S-transferase Gene Superfamily Widely Exists in Nonplant Taxonomic Groups. Evol Bioinform Online. 2016 Feb 10;12:59-71. PMID:26884677 doi:10.4137/EBO.S35909
  13. ↑ Morgenstern R, Zhang J, Johansson K. Microsomal glutathione transferase 1: mechanism and functional roles. Drug Metab Rev. 2011 May;43(2):300-6. PMID:21495795 doi:10.3109/03602532.2011.558511
  14. ↑ Rossjohn J, Feil SC, Wilce MC, Sexton JL, Spithill TW, Parker MW. Crystallization, structural determination and analysis of a novel parasite vaccine candidate: Fasciola hepatica glutathione S-transferase. J Mol Biol. 1997 Nov 7;273(4):857-72. PMID:9367777 doi:10.1006/jmbi.1997.1338

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Michal Harel, Alexander Berchansky

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