586
Views
26
CrossRef citations to date
0
Altmetric
Review Article

Human cytosolic glutathione-S-transferases: quantitative analysis of expression, comparative analysis of structures and inhibition strategies of isozymes involved in drug resistance

&
Pages 318-337 | Received 19 Apr 2017, Accepted 12 Jun 2017, Published online: 12 Jul 2017

References

  • Aceto, A., et al., 1997. Identification of an N-capping box that affects the α6-helix propensity in glutathione S-transferase superfamily proteins: a role for an invariant aspartic residue. Biochemical journal, 322, 229–234.
  • Adang, A.E., et al., 1990. The glutathione-binding site in glutathione S-transferases. Investigation of the cysteinyl, glycyl and gamma-glutamyl domains. Biochemical journal, 269, 47–54.
  • Adler, V., et al., 1999. Regulation of JNK signaling by GSTp. The EMBO journal, 18, 1321–1334.
  • Allardyce, C.S., et al., 1999. The role of tyrosine-9 and the C-terminal helix in the catalytic mechanism of alpha-class glutathione S-transferases. Biochemical journal, 343, 525–531.
  • Allocati, N., et al., 1999. Functional analysis of the evolutionarily conserved proline 53 residue in Proteus mirabilis glutathione transferase B1-1. FEBS letters, 445, 347–350.
  • Alparslan, M.M. and Danış, Ö., 2015. In vitro inhibition of human placental glutathione S-transferase by 3-arylcoumarin derivatives. Archiv der pharmazie, 348, 635–642.
  • Alves, C.S., et al., 2006. The intersubunit lock-and-key motif in human glutathione transferase A1-1: role of the key residues Met(51) and Phe(52) in function and dimer stability. Biochemical journal, 393, 523–528.
  • Aniya, Y. and Imaizumi, N., 2011. Mitochondrial glutathione transferases involving a new function for membrane permeability transition pore regulation. Drug Metabolism Reviews, 43, 292–299.
  • Anttila, S., et al., 1993. Immunohistochemical localization of glutathione S-transferases in human lung. International journal of cancer research, 53, 5643–5648.
  • Armstrong, R.N., 1991. Glutathione S-transferases: reaction mechanism, structure, and function. Chemical research in toxicology, 4, 131–140.
  • Ascione, A., et al., 2009. The glutathione S-transferase inhibitor 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol overcomes the MDR1-P-glycoprotein and MRP1-mediated multidrug resistance in acute myeloid leukemia cells. Cancer chemotherapy and pharmacology, 64, 419–424.
  • Athar, A. and Chibuike, C.U., 2008. The discovery and application of inhibitors of glutathione S-transferase as therapeutic agents – a review. Current bioactive compounds, 4, 41–50.
  • Atkins, W.M., et al., 1993. The catalytic mechanism of glutathione S-transferase (GST). Spectroscopic determination of the pKa of Tyr-9 in rat alpha 1-1 GST. The journal of biological chemistry, 268, 19188–19191.
  • Berman, H.M., et al., 2000. The Protein Data Bank. Nucleic acids research, 28, 235–242.
  • Blackburn, A.C., et al., 2006. Deficiency of glutathione transferase zeta causes oxidative stress and activation of antioxidant response pathways. Molecular pharmacology, 69, 650–657.
  • Board, P.G., 2011. The omega-class glutathione transferases: structure, function, and genetics. Drug metabolism reviews, 43, 226–235.
  • Board, P.G., Coggan, M., and Chelvanayagam, G., 2000a. Identification, characterization, and crystal structure of the omega class glutathione transferases. The journal of biological chemistry, 275, 24798–24806.
  • Board, P.G., et al., 1997. Zeta, a novel class of glutathione transferases in a range of species from plants to humans. Biochemical journal, 328, 929–935.
  • Board, P.G., et al., 2000b. Identification, characterization, and crystal structure of the omega class glutathione transferases. Journal of biological chemistry, 275, 24798–24806.
  • Booth, J., Boyland, E., and Sims, P., 1961. An enzyme from rat liver catalysing conjugations with glutathione. The biochemical journal, 79, 516–524.
  • Burg, D., et al., 2002. Peptidomimetic glutathione analogues as novel γGT stable GST inhibitors. Bioorganic & medicinal chemistry, 10, 195–205.
  • Caccuri, A.M., et al., 1996. Structural flexibility modulates the activity of human glutathione transferase P1-1: influence of a poor co-substrate on dynamics and kinetics of human glutathione transferase. Journal of biological chemistry, 271, 16193–16198.
  • Caccuri, A.M., et al., 1997. Catalytic mechanism and role of hydroxyl residues in the active site of theta class glutathione S-transferases. Investigation of Ser-9 and Tyr-113 in a glutathione S-transferase from the Australian sheep blowfly, Lucilia Cuprina, The journal of biological chemistry, 272, 29681–29686.
  • Cameron, A.D., et al., 1995. Structural analysis of human alpha-class glutathione transferase A1-1 in the apo-form and in complexes with ethacrynic acid and its glutathione conjugate. Structure, 3, 717–727.
  • Cao, W., Zuo, J., and Fang, F., 1999. Role of glutathione S-transferase pi in tumor drug resistance. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta academiae medicinae sinicae, 21, 402–406.
  • Carder, P.J., et al., 1990. Glutathione S-transferase in human brain. Neuropathology and applied neurobiology, 16, 293–303.
  • Cazenave, L.A., et al., 1989. Glutathione S-transferase and drug resistance. Cancer treatment and research, 48, 171–187.
  • Chuang, S.T., et al., 2005. Overexpression of glutathione s-transferase alpha in clear cell renal cell carcinoma. American journal of clinical pathology, 123, 421–429.
  • Combes, B. and Stakelum, G.S., 1961. A liver enzyme that conjugates sulfobromophthalein sodium with glutathione. Journal of clinical investigation, 40, 981–988.
  • Crawford, L.A. and Weerapana, E., 2016. A tyrosine-reactive irreversible inhibitor for glutathione S-transferase Pi (GSTP1). Molecular biosystems, 12, 1768–1771.
  • Dalle-Donne, I., et al., 2009. Protein S-glutathionylation: a regulatory device from bacteria to humans. Trends in biochemical sciences, 34, 85–96.
  • Daniel, F.A.R.D., Pedro Alexandrino, F., and Maria Joao, R., 2008. Mammalian cytosolic glutathione transferases. Current protein & peptide science, 9, 325–337.
  • Das, M., Bickers, D.R., and Mukhtar, H., 1984. Plant phenols as in vitro inhibitors of glutathione S-transferase(s). Biochemical and biophysical research communications, 120, 427–433.
  • de Oliveira, D.M., et al., 2014a. 8-Methoxypsoralen is a competitive inhibitor of glutathione S-transferase P1-1. Frontiers in cellular neuroscience, 8, 308.
  • de Waart, F.G., et al., 2001. Effect of glutathione S-transferase M1 genotype on progression of atherosclerosis in lifelong male smokers. Atherosclerosis, 158, 227–231.
  • Dirr, H., Reinemer, P., and Huber, R., 1994. X-ray crystal structures of cytosolic glutathione S-transferases. Implications for protein architecture, substrate recognition and catalytic function. European journal of biochemistry, 220, 645–661.
  • Dirr, H.W., et al., 2005. A conserved N-capping motif contributes significantly to the stabilization and dynamics of the C-terminal region of class alpha glutathione S-transferases. Journal of biological chemistry, 280, 19480–19487.
  • Dragani, B., et al., 1997. The conserved N-capping box in the hydrophobic core of glutathione S-transferase P1–1 is essential for refolding: identification of a buried and conserved hydrogen bond important for protein stability. Journal of biological chemistry, 272, 25518–25523.
  • Dulhunty, A.F., et al., 2011. Regulation of the cardiac muscle ryanodine receptor by glutathione transferases. Drug metabolism reviews, 43, 236–252.
  • Edgar, R.C., 2004. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC bioinformatics, 5, 113.
  • Evangelia, E.L. and Nikolaos, G.C., 2009. Glutathione transferases: emerging multidisciplinary tools in red and green biotechnology. Recent patents on biotechnology, 3, 211–223.
  • Ezer, R., et al., 2002. Identification of glutathione S-transferase (GST) polymorphisms in brain tumors and association with susceptibility to pediatric astrocytomas. Journal of neuro-oncology, 59, 123–134.
  • Fagerberg, L., et al., 2014. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Molecular & cellular proteomics, 13, 397–406.
  • Federici, L., et al., 2009. Structural basis for the binding of the anticancer compound 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol to human glutathione s-transferases. Cancer research, 69, 8025–8034.
  • Findlay, V.J., et al., 2004. Tumor cell responses to a novel glutathione S-transferase-activated nitric oxide-releasing prodrug. Molecular pharmacology, 65, 1070–1079.
  • Flatgaard, J.E., Bauer, K.E., and Kauvar, L.M., 1993. Isozyme specificity of novel glutathione-S-transferase inhibitors. Cancer chemotherapy and pharmacology, 33, 63–70.
  • Fletcher, M.E., et al., 2015. Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism. American journal of physiology – lung cellular and molecular physiology, 308, L1274–L1285.
  • Giffen, P.S., et al., 2002. Alpha-glutathione S-transferase in the assessment of hepatotoxicity–its diagnostic utility in comparison with other recognized markers in the Wistar Han rat. Toxicologic pathology, 30, 365–372.
  • Grahn, E., et al., 2006. New crystal structures of human glutathione transferase A1-1 shed light on glutathione binding and the conformation of the C-terminal helix. Acta crystallographica section D: biological crystallography, 62, 197–207.
  • Habig, W.H. and Jakoby, W.B., 1981. Assays for differentiation of glutathione S-transferases. Methods in enzymology, 77, 398–405.
  • Habig, W.H., et al., 1974. The identity of glutathione S-transferase B with ligandin, a major binding protein of liver. Proceedings of the national academy of sciences of the United States of America, 71, 3879–3882.
  • Harrison, D.J., et al., 1990. Glutathione S-transferases in alcoholic liver disease. Gut, 31, 909–912.
  • Harshbarger, W., et al., 2016. Structural and biochemical analyses reveal the mechanism of glutathione S-transferase Pi 1 inhibition by the anti-cancer compound piperlongumine. Journal of biological chemistry, 292, 112–120.
  • Hayes, J.D., Flanagan, J.U., and Jowsey, I.R., 2005. Glutathione transferases. Annual review of pharmacology and toxicology, 45, 51–88.
  • Hayes, J.D. and Pulford, D.J., 1995. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Critical reviews in biochemistry and molecular biology, 30, 445–600.
  • Hayes, J.D. and Strange, R.C., 1995. Potential contribution of the glutathione S-transferase supergene family to resistance to oxidative stress. Free radical research, 22, 193–207.
  • Hayeshi, R., et al., 2007. The inhibition of human glutathione S-transferases activity by plant polyphenolic compounds ellagic acid and curcumin. Food and chemical toxicology, 45, 286–295.
  • Hegazy, U.M., Mannervik, B., and Stenberg, G., 2004. Functional role of the lock and key motif at the subunit interface of glutathione transferase P1-1. Journal of biological chemistry, 279, 9586–9596.
  • Hitchens, T.K., Mannervik, B., and Rule, G.S., 2001. Disorder-to-order transition of the active site of human class Pi glutathione transferase, GST P1-1. Biochemistry, 40, 11660–11669.
  • Hohwy, M., et al., 2008. Novel prostaglandin D synthase inhibitors generated by fragment-based drug design. Journal of medicinal chemistry, 51, 2178–2186.
  • Honaker, M.T., et al., 2013. Enzymatic detoxication, conformational selection, and the role of molten globule active sites. The journal of biological chemistry, 288, 18599–18611.
  • Hou, L., et al., 2007. Functional promiscuity correlates with conformational heterogeneity in A-class glutathione S-transferases, Journal of biological chemistry, 282, 23264–23274.
  • Hubatsch, I., Ridderström, M., and Mannervik, B., 1998. Human glutathione transferase A4-4: an alpha class enzyme with high catalytic efficiency in the conjugation of 4-hydroxynonenal and other genotoxic products of lipid peroxidation. Biochemical journal, 330, 175–179.
  • Iersel, MLPSv., et al., 1996. Inhibition of glutathione S-transferase activity in human melanoma cells by alfa, beta-unsaturated carbonyl derivatives: effects of acrolein, cinnamaldehyde, citral, crotonaldehyde, curcumin, ethacrynic acid, and trans-2-hexenal. Chemico-biological interactions 102, 117–132.
  • Inoue, T., et al., 2003. Mechanism of metal activation of human hematopoietic prostaglandin D synthase. Nature structural biology, 10, 291–296.
  • Jakobsson, P.-J., et al., 1999. Common structural features of mapeg—a widespread superfamily of membrane associated proteins with highly divergent functions in eicosanoid and glutathione metabolism. Protein science, 8, 689–692.
  • Jakoby, W.B., 1978. The glutathione S-transferases: a group of multifunctional detoxification proteins. Advances in enzymology and related areas of molecular biology, 46, 383–414.
  • Ji, X., et al., 1997. Structure and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione S-transferase. Biochemistry, 36, 9690–9702.
  • Johansson, A.-S. and Mannervik, B., 2001. Human glutathione transferase A3-3, a highly efficient catalyst of double-bond isomerization in the biosynthetic pathway of steroid hormones. Journal of biological chemistry, 276, 33061–33065.
  • Jones, J.T., et al., 2016. Glutathione S-transferase pi modulates NF-κB activation and pro-inflammatory responses in lung epithelial cells. Redox biology, 8, 375–382.
  • Jowsey, I.R., et al., 2001. Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases. Biochemical journal, 359, 507–516.
  • Kalinina, E.V., et al., 2007. Expression of genes for redox-dependent glutathione S-transferase isoforms GSTP1-1 and GSTA4-4 in tumor cell during the development doxorubicin resistance. Bulletin of experimental biology and medicine, 143, 328–330.
  • Kalinina, E.V., et al., 2012. Expression of genes of glutathione transferase isoforms GSTP1-1, GSTA4-4, and GSTK1-1 in tumor cells during the formation of drug resistance to cisplatin. Bulletin of experimental biology and medicine, 154, 64–67.
  • Kanaoka, Y., et al., 1998. Cloning and crystal structure of hematopoietic prostaglandin D synthase. Cell, 90, 1085–1095.
  • Ketley, J.N., Habig, W.H., and Jakoby, W.B., 1975. Binding of nonsubstrate ligands to the glutathione S-transferases. The journal of biological chemistry, 250, 8670–8673.
  • Ketterer, B., 1988. Protective role of glutathione and glutathione transferases in mutagenesis and carcinogenesis. Mutation research, 202, 343–361.
  • Kim, S.J. and Lee, S.G. 2007. PI3K, RSK, and mTOR signal networks for the GST gene regulation. Toxicological sciences: an official journal of the society of toxicology, 96, 206–213.
  • Klys, H.S., et al., 1992. Glutathione S-transferase expression in the human testis and testicular germ cell neoplasia. British journal of cancer, 66 (3), 589–593.
  • Knight, T.R., Choudhuri, S., and Klaassen, C.D., 2007. Constitutive mRNA expression of various glutathione S-transferase isoforms in different tissues of mice. Toxicological sciences, 100, 513–524.
  • Krajinovic, M., Labuda, D., and Sinnett, D., 2002. Glutathione S-transferase P1 genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukaemia. Pharmacogenetics, 12, 655–658.
  • Kumar, V., et al., 2010. Stabilization of the nitric oxide (NO) prodrugs and anti-cancer leads, PABA/NO and double JS-K through incorporation into PEG-protected nanoparticles. Molecular pharmaceutics, 7, 291.
  • Kumari, V., et al., 2016. Irreversible inhibition of glutathione S-transferase by phenethyl isothiocyanate (PEITC), a dietary cancer chemopreventive phytochemical. PLoS one, 11, e0163821.
  • Laborde, E., 2010. Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death. Cell death and differentiation, 17, 1373–1380.
  • Le Trong, I., et al., 2002. 1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site. Proteins, 48, 618–627.
  • Li, R., et al., 2017. Glutathione S-transferase A1 (GSTA1) as a marker of acetaminophen-induced hepatocyte injury in vitro. Toxicology mechanisms and methods, 27, 401–407.
  • Li, W., et al., 2015. The EMBL-EBI bioinformatics web and programmatic tools framework. Nucleic acids research, 43, W580–W584.
  • Ligand Explorer (LigPro) Home page[http://ligpro.sdsc.edu].
  • Lin, C.-Y., et al., 2017. Inhibition of JNK by pi class of glutathione S-transferase through PKA/CREB pathway is associated with carnosic acid protection against 6-hydroxydopamine-induced apoptosis. Food and chemical toxicology, 103, 194–202.
  • Litwack, G., Ketterer, B., and Arias, I.M., 1971. Ligandin: a hepatic protein which binds steroids, bilirubin, carcinogens and a number of exogenous organic anions. Nature, 234, 466–467.
  • Liu, D., et al., 2009. Dissection of the inhibition of cardiac ryanodine receptors by human glutathione transferase GSTM2-2. Biochemical pharmacology, 77, 1181–1193.
  • Liu, S., Stoesz, S.P., and Pickett, C.B., 1998. Identification of a novel human glutathione S-transferase using bioinformatics. Archives of biochemistry and biophysics, 352, 306–313.
  • Lo, H.-W., and Ali-Osman, F., 2007. Genetic polymorphism and function of glutathione S-transferases in tumor drug resistance. Current opinion in pharmacology, 7, 367–374.
  • Lyon, R.P., Hill, J.J., and Atkins, W.M., 2003. Novel class of bivalent glutathione S-transferase inhibitors. Biochemistry, 42, 10418–10428.
  • Lyttle, M.H., et al., 1994. Glutathione-S-transferase activates novel alkylating agents. Journal of medicinal chemistry, 37, 1501–1507.
  • Maeda, D.Y., et al., 2006. Bivalent inhibitors of glutathione S-transferase: the effect of spacer length on isozyme selectivity. Bioorganic & medicinal chemistry letters, 16, 3780–3783.
  • Mannervik, B., et al., 1992. Nomenclature for human glutathione transferases. Biochemical journal, 282, 305–306.
  • Martin, J.L., 1995. Thioredoxin – a fold for all reasons. Structure, 3, 245–250.
  • Mathew, N., Kalyanasundaram, M., and Balaraman, K., 2006. Glutathione S-transferase (GST) inhibitors. Expert opinion on therapeutic patents, 16, 431–444.
  • McIlwain, C.C., Townsend, D.M., and Tew, K.D., 2006. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene, 25, 1639–1648.
  • McMillan, D.H., et al., 2016. Attenuation of lung fibrosis in mice with a clinically relevant inhibitor of glutathione-S-transferase π. JCI insight, 1, e85717.
  • Menegon, A., et al., 1998. Parkinson's disease, pesticides, and glutathione transferase polymorphisms. The Lancet, 352, 1344–1346.
  • Mileo, A.M., et al., 2009. Human papillomavirus-16 E7 interacts with glutathione S-transferase P1 and enhances its role in cell survival. PLoS one, 4, e7254
  • Mitchell, A.E., et al., 1997. Quantitative profiling of tissue- and gender-related expression of glutathione S-transferase isoenzymes in the mouse. Biochemical journal, 325, 207–216.
  • Monks, T.J., et al., 1990. Glutathione conjugate mediated toxicities. Toxicology and applied pharmacology, 106, 1–19.
  • Morel, F., et al., 2002. The human glutathione transferase alpha locus: genomic organization of the gene cluster and functional characterization of the genetic polymorphism in the hGSTA1 promoter. Pharmacogenetics, 12, 277–286.
  • Morel, F., et al., 2004. Gene and protein characterization of the human glutathione S-transferase kappa and evidence for a peroxisomal localization, Journal of biological chemistry, 279, 16246–16253.
  • Morris, M.J., et al., 2011. A structural basis for cellular uptake of GST-fold proteins. PLoS one, 6, e17864
  • Moscow, J.A., Townsend, A.J., and Cowan, K.H., 1989. Elevation of pi class glutathione S-transferase activity in human breast cancer cells by transfection of the GST pi gene and its effect on sensitivity to toxins. Molecular pharmacology, 36, 22–28.
  • Mukanganyama, S., et al., 2002. Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. International journal of cancer, 97, 700–705.
  • Najmanovich, R.J., et al., 2013. Drug promiscuity in PDB: protein binding site similarity is key. PLoS one, 8, e65894.
  • NCBI, 2017. Database Resources of the National Center for Biotechnology Information. Nucleic acids research, 45, D12–D17.
  • Nebert, D.W. and Vasiliou, V., 2004. Analysis of the glutathione S-transferase (GST) gene family. Human genomics, 1, 460.
  • Nieslanik, B.S., Ibarra, C., and Atkins, W.M., 2001. The C-terminus of glutathione S-transferase A1-1 is required for entropically-driven ligand binding. Biochemistry, 40, 3536–3543.
  • Oakley, A., 2011. Glutathione transferases: a structural perspective. Drug metabolism reviews, 43, 138–151.
  • Ouwerkerk-Mahadevan, S., et al., 1995. Glutathione analogues as novel inhibitors of rat and human glutathione S-transferase isoenzymes, as well as of glutathione conjugation in isolated rat hepatocytes and in the rat in vivo. Biochemical journal, 308 (1), 283–290.
  • Pan, X.D., et al., 2014. Expression and function of GSTA1 in lung cancer cells. Asian Pacific journal of cancer prevention: APJCP, 15, 8631–8635.
  • Parker, L.J., et al., 2011. Studies of glutathione transferase P1-1 bound to a platinum(IV)-based anticancer compound reveal the molecular basis of its activation. Chemistry – a European journal, 17, 7806–7816.
  • Patskovsky, Y., et al., 2006. Transition state model and mechanism of nucleophilic aromatic substitution reactions catalyzed by human glutathione S-transferase M1a-1a. Biochemistry, 45, 3852–3862.
  • Patskovsky, Y.V., Patskovska, L.N., and Listowsky, I., 1999. Functions of His107 in the catalytic mechanism of human glutathione S-transferase hGSTM1a-1a. Biochemistry, 38, 1193–1202.
  • Pemble, S.E. and Taylor, J.B., 1992. An evolutionary perspective on glutathione transferases inferred from class-theta glutathione transferase cDNA sequences. Biochemical journal, 287, 957–963.
  • Pettersen, E.F., et al., 2004. UCSF Chimera – a visualization system for exploratory research and analysis. Journal of computational chemistry, 25, 1605–1612.
  • Polekhina, G., et al., 2001. Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity. Biochemistry, 40, 1567–1576.
  • Polidoro, G., et al., 1984. In vitro interaction of penicillins and cephalosporins with human placenta GSH S-transferase. Research communications in chemical pathology and pharmacology, 46, 411–423.
  • Prade, L., et al., 1997. Structures of class pi glutathione S-transferase from human placenta in complex with substrate, transition-state analogue and inhibitor. Structure, 5, 1287–1295.
  • Raza, H., 2011. Dual localization of glutathione S-transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease. FEBS journal, 278, 4243–4251.
  • Reinemer, P., et al., 1992. Three-dimensional structure of class pi glutathione S-transferase from human placenta in complex with S-hexylglutathione at 2.8 A resolution. Journal of molecular biology, 227, 214–226.
  • Richardson, J.S. and Richardson, D.C., 1988. Amino acid preferences for specific locations at the ends of alpha helices. Science (New York, N.Y.), 240, 1648–1652.
  • Romero, L., et al., 2006. Human GSTA1-1 reduces c-Jun N-terminal kinase signalling and apoptosis in Caco-2 cells. Biochemical journal, 400, 135–141.
  • Rossjohn, J., et al., 1998. Human theta class glutathione transferase: the crystal structure reveals a sulfate-binding pocket within a buried active site. Structure, 6, 309–322.
  • Ruzza, P. and Calderan, A., 2013. Glutathione transferase (GST)-activated prodrugs. Pharmaceutics, 5, 220–231.
  • Sarkar, D., et al., 2001. Overexpression of glutathione-S-transferase A1 in benign adrenocortical adenomas from patients with Cushing’s syndrome. The journal of clinical endocrinology & metabolism, 86, 1653–1659.
  • Sato, K., Tsuchida, S., and Tamai, K., 1989. Anti-cancer drug resistance and glutathione S-transferases. Gan to Kagaku Ryoho. Cancer & chemotherapy, 16, 592–598.
  • Sau, A., et al., 2010. Glutathione transferases and development of new principles to overcome drug resistance. Archives of biochemistry and biophysics, 500, 116–122.
  • Sawers, L., et al., 2014. Glutathione S-transferase P1 (GSTP1) directly influences platinum drug chemosensitivity in ovarian tumour cell lines. British journal of cancer, 111, 1150–1158.
  • Sayed, Y., Wallace, L.A., and Dirr, H.W., 2000. The hydrophobic lock-and-key intersubunit motif of glutathione transferase A1-1: implications for catalysis, ligandin function and stability. FEBS letters, 465, 169–172.
  • Schultz, M., Dutta, S., and Tew, K.D., 1997. Inhibitors of glutathione S-transferases as therapeutic agents. Advanced drug delivery reviews, 26, 91–104.
  • Seitz, G., et al., 2010. Inhibition of glutathione-S-transferase as a treatment strategy for multidrug resistance in childhood rhabdomyosarcoma. International journal of oncology, 36, 491–500.
  • Shang, W., et al., 2008. Expressions of glutathione S-transferase alpha, mu, and pi in brains of medically intractable epileptic patients. BMC neuroscience, 9, 67-67.
  • Sharma, R., et al., 2004. Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxidants & redox signaling, 6, 289–300.
  • Shi, M., et al., 2009. Identification of glutathione S-transferase Pi as a protein involved in Parkinson disease progression. The American journal of pathology, 175, 54–65.
  • Simic, T., et al., 2009. Glutathione S-transferases in kidney and urinary bladder tumors. Nature reviews urology, 6, 281–289.
  • Singh, S.P., Zimniak, L., and Zimniak, P., 2010. The human hGSTA5 gene encodes an enzymatically active protein. Biochimica et biophysica acta, 1800, 16–22.
  • Stenberg, G., et al., 2000. A conserved “hydrophobic staple motif” plays a crucial role in the refolding of human glutathione transferase P1-1. Journal of biological chemistry, 275, 10421–10428.
  • Stoehlmacher, J., et al., 2002. Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. Cancer spectrum knowledge environment institute, 94, 936–942.
  • Sun, K.H., et al., 2011. Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase activity. Journal of neurochemistry, 118, 902–914.
  • Tars, K., et al., 2006. Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant. Journal of molecular biology, 355, 96–105.
  • Tew, K.D. and Townsend, D.M., 2011. Regulatory functions of glutathione S-transferase P1-1 unrelated to detoxification. Drug metabolism reviews, 43, 179–193.
  • Theodoratos, A., et al., 2009. Phenylalanine-induced leucopenia in genetic and dichloroacetic acid generated deficiency of glutathione transferase Zeta. Biochemical pharmacology, 77, 1358–1363.
  • Townsend, D. and Tew, K., 2003a. Cancer drugs, genetic variation, and the glutathione-S-transferase gene family. American journal of Pharmacogenomics, 3, 157–172.
  • Townsend, D.M. and Tew, K.D., 2003b. The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene, 22, 7369–7375.
  • Townsend, D.M., et al., 2002. Efficacy of a glutathione S-transferase π-activated prodrug in platinum-resistant ovarian cancer cells. Molecular cancer therapeutics, 1, 1089–1095.
  • Tsuchida, S. and Sato, K., 1992. Glutathione transferases and cancer. Critical reviews in biochemistry and molecular biology, 27, 337–384.
  • Turella, P., et al., 2005. Proapoptotic activity of new glutathione S-transferase inhibitors. Cancer research, 65, 3751–3761.
  • van Bladeren, P.J. and van Ommen, B., 1991. The inhibition of glutathione S-transferases: mechanisms, toxic consequences and therapeutic benefits. Pharmacology & therapeutics, 51, 35–46.
  • Wang, B., et al., 2011. Crystal structures and kinetic studies of human Kappa class glutathione transferase provide insights into the catalytic mechanism. Biochemical journal, 439, 215–225.
  • Wang, X., Yang, Y. and Huycke, M., 2013. Abstract 1344: glutathione-S transferase alpha 4 is a potential biomarker for Enterococcus faecalis-induced inflammation and colon cancer. Cancer research, 73, 1344–1344.
  • Wang, Z., et al., 2015. Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis. Scientific reports, 5, 9301.
  • Wilce, M.C.J. and Parker, M.W., 1994. Structure and function of glutathione S-transferases. Biochimica et biophysica acta (BBA) – protein structure and molecular enzymology, 1205, 1–18.
  • Wu, B. and Dong, D., 2012. Human cytosolic glutathione transferases: structure, function, and drug discovery. Trends in pharmacological sciences, 33, 656–668.
  • Yang, Y., et al., 2004. Glutathione-S-transferase A4-4 modulates oxidative stress in endothelium: possible role in human atherosclerosis. Atherosclerosis, 173, 211–221.
  • Yang, Y., et al., 2016. Glutathione S-transferase alpha 4 induction by activator protein 1 in colorectal cancer. Oncogene, 35, 5795–5806.
  • Yates, A., et al., 2016. Ensembl 2016. Nucleic acids research, 44, D710–D716.
  • Zhan, Y. and Rule, G.S., 2004. Glutathione induces helical formation in the carboxy terminus of human glutathione transferase A1-1. Biochemistry, 43, 7244–7254.
  • Zhang, J., et al., 2014. Pleiotropic functions of glutathione S-transferase P. Advances in cancer research, 122, 143–175.
  • Zhao, T., et al., 1999. The role of human glutathione S-transferases hGSTA1-1 and hGSTA2-2 in protection against oxidative stress. Archives of biochemistry and biophysics, 367, 216–224.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.