PDBsum entry 2ljr

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Transferase PDB id
Protein chains
244 a.a. *
Waters ×2
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Glutathione transferase apo-form from human
Structure: Glutathione s-transferase. Chain: a, b. Synonym: hgst t2-2. Engineered: yes. Other_details: apo form
Source: Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
3.20Å     R-factor:   0.200     R-free:   0.291
Authors: J.Rossjohn,W.J.Mckinstry,A.J.Oakley,D.Verger,J.Flanagan, G.Chelvanayagam,K.L.Tan,P.G.Board,M.W.Parker
Key ref:
J.Rossjohn 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. PubMed id: 9551553 DOI: 10.1016/S0969-2126(98)00034-3
08-Mar-98     Release date:   23-Mar-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0CG30  (GSTT2_HUMAN) -  Glutathione S-transferase theta-2B
244 a.a.
244 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
+ glutathione
= HX
+ R-S-glutathione
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   4 terms 
  Biological process     small molecule metabolic process   3 terms 
  Biochemical function     transferase activity     2 terms  


DOI no: 10.1016/S0969-2126(98)00034-3 Structure 6:309-322 (1998)
PubMed id: 9551553  
Human theta class glutathione transferase: the crystal structure reveals a sulfate-binding pocket within a buried active site.
J.Rossjohn, W.J.McKinstry, A.J.Oakley, D.Verger, J.Flanagan, G.Chelvanayagam, K.L.Tan, P.G.Board, M.W.Parker.
BACKGROUND: Glutathione S-transferases (GSTs) comprise a multifunctional group of enzymes that play a critical role in the cellular detoxification process. These enzymes reduce the reactivity of toxic compounds by catalyzing their conjugation with glutathione. As a result of their role in detoxification, GSTs have been implicated in the development of cellular resistance to antibiotics, herbicides and clinical drugs and their study is therefore of much interest. In mammals, the cytosolic GSTs can be divided into five distinct classes termed alpha, mu, pi, sigma and theta. The human theta class GST, hGST T2-2, possesses several distinctive features compared to GSTs of other classes, including a long C-terminal extension and a specific sulfatase activity. It was hoped that the determination of the structure of hGST T2-2 may help us to understand more about this unusual class of enzymes. RESULTS: Here we present the crystal structures of hGST T2-2 in the apo form and in complex with the substrates glutathione and 1-menaphthyl sulfate. The enzyme adopts the canonical GST fold with a 40-residue C-terminal extension comprising two helices connected by a long loop. The extension completely buries the substrate-binding pocket and occludes most of the glutathione-binding site. The enzyme has a purpose-built novel sulfate-binding site. The crystals were shown to be catalytically active: soaks with 1-menaphthyl sulfate result in the production of the glutathione conjugate and cleavage of the sulfate group. CONCLUSIONS: hGST T2-2 shares less than 15% sequence identity with other GST classes, yet adopts a similar three-dimensional fold. The C-terminal extension that blocks the active site is not disordered in either the apo or complexed forms of the enzyme, but nevertheless catalysis occurs in the crystalline state. A narrow tunnel leading from the active site to the surface may provide a pathway for the entry of substrates and the release of products. The results suggest a molecular basis for the unique sulfatase activity of this GST.
  Selected figure(s)  
Figure 4.
Figure 4. Surface representations [52] of GST structures from each class highlighting the C-terminal tails in red. GSH is shown in ball-and-stick form in each figure with atoms depicted in standard colors. GSH is bound in the G site and the H site is located adjacent to it with the C-terminal tail forming part of the H-site wall. (a) Human theta class hGST T2-2. (b) Human alpha class A1-1 [23]. (c) Insect theta class GST [19]. (d) Rat mu class M3-3 [24]. (e) Human pi class P1-1 [26]. (f) Squid sigma class [25].
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 309-322) copyright 1998.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21428697 A.Oakley (2011).
Glutathione transferases: a structural perspective.
  Drug Metab Rev, 43, 138-151.  
  21425928 J.U.Flanagan, and M.L.Smythe (2011).
Sigma-class glutathione transferases.
  Drug Metab Rev, 43, 194-214.  
  21435060 K.Yamamoto, S.Teshiba, Y.Shigeoka, Y.Aso, Y.Banno, T.Fujiki, and Y.Katakura (2011).
Characterization of an omega-class glutathione S-transferase in the stress response of the silkmoth.
  Insect Mol Biol, 20, 379-386.  
  20981235 P.D.Josephy (2010).
Genetic variations in human glutathione transferase enzymes: significance for pharmacology and toxicology.
  Hum Genomics Proteomics, 2010, 876940.  
19424424 Y.Zhao, M.Marotta, E.E.Eichler, C.Eng, and H.Tanaka (2009).
Linkage disequilibrium between two high-frequency deletion polymorphisms: implications for association studies involving the glutathione-S transferase (GST) genes.
  PLoS Genet, 5, e1000472.  
17682821 B.Blanchette, X.Feng, and B.R.Singh (2007).
Marine glutathione S-transferases.
  Mar Biotechnol (NY), 9, 513-542.  
17284839 K.Yamamoto, H.Fujii, Y.Aso, Y.Banno, and K.Koga (2007).
Expression and characterization of a sigma-class glutathione S-transferase of the fall webworm, Hyphantria cunea.
  Biosci Biotechnol Biochem, 71, 553-560.  
16189827 D.J.Schuller, Q.Liu, I.A.Kriksunov, A.M.Campbell, J.Barrett, P.M.Brophy, and Q.Hao (2005).
Crystal structure of a new class of glutathione transferase from the model human hookworm nematode Heligmosomoides polygyrus.
  Proteins, 61, 1024-1031.
PDB code: 1tw9
16195232 E.Cesareo, L.J.Parker, J.Z.Pedersen, M.Nuccetelli, A.P.Mazzetti, A.Pastore, G.Federici, A.M.Caccuri, G.Ricci, J.J.Adams, M.W.Parker, and M.Lo Bello (2005).
Nitrosylation of human glutathione transferase P1-1 with dinitrosyl diglutathionyl iron complex in vitro and in vivo.
  J Biol Chem, 280, 42172-42180.
PDB code: 1zgn
16081649 J.Li, Z.Xia, and J.Ding (2005).
Thioredoxin-like domain of human kappa class glutathione transferase reveals sequence homology and structure similarity to the theta class enzyme.
  Protein Sci, 14, 2361-2369.
PDB code: 1yzx
16012173 P.Winayanuwattikun, and A.J.Ketterman (2005).
An electron-sharing network involved in the catalytic mechanism is functionally conserved in different glutathione transferase classes.
  J Biol Chem, 280, 31776-31782.  
15621414 S.McGoldrick, S.M.O'Sullivan, and D.Sheehan (2005).
Glutathione transferase-like proteins encoded in genomes of yeasts and fungi: insights into evolution of a multifunctional protein superfamily.
  FEMS Microbiol Lett, 242, 1.  
14713336 A.P.Fernandes, and A.Holmgren (2004).
Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a simple thioredoxin backup system.
  Antioxid Redox Signal, 6, 63-74.  
12871945 F.De Maria, J.Z.Pedersen, A.M.Caccuri, G.Antonini, P.Turella, L.Stella, M.Lo Bello, G.Federici, and G.Ricci (2003).
The specific interaction of dinitrosyl-diglutathionyl-iron complex, a natural NO carrier, with the glutathione transferase superfamily: suggestion for an evolutionary pressure in the direction of the storage of nitric oxide.
  J Biol Chem, 278, 42283-42293.  
12972429 M.G.Jeppesen, P.Ortiz, W.Shepard, T.G.Kinzy, J.Nyborg, and G.R.Andersen (2003).
The crystal structure of the glutathione S-transferase-like domain of elongation factor 1Bgamma from Saccharomyces cerevisiae.
  J Biol Chem, 278, 47190-47198.
PDB code: 1nhy
12439221 A.K.Alexandrie, A.Rannug, E.Juronen, G.Tasa, and M.Warholm (2002).
Detection and characterization of a novel functional polymorphism in the GSTT1 gene.
  Pharmacogenetics, 12, 613-619.  
11741965 A.Vlamis-Gardikas, A.Potamitou, R.Zarivach, A.Hochman, and A.Holmgren (2002).
Characterization of Escherichia coli null mutants for glutaredoxin 2.
  J Biol Chem, 277, 10861-10868.  
12144922 X.Ren, P.Jemth, P.G.Board, G.Luo, B.Mannervik, J.Liu, K.Zhang, and J.Shen (2002).
A semisynthetic glutathione peroxidase with high catalytic efficiency. Selenoglutathione transferase.
  Chem Biol, 9, 789-794.  
11604524 A.J.Oakley, T.Harnnoi, R.Udomsinprasert, K.Jirajaroenrat, A.J.Ketterman, and M.C.Wilce (2001).
The crystal structures of glutathione S-transferases isozymes 1-3 and 1-4 from Anopheles dirus species B.
  Protein Sci, 10, 2176-2185.
PDB codes: 1jlv 1jlw
11453994 D.Gisi, J.Maillard, J.U.Flanagan, J.Rossjohn, G.Chelvanayagam, P.G.Board, M.W.Parker, T.Leisinger, and S.Vuilleumier (2001).
Dichloromethane mediated in vivo selection and functional characterization of rat glutathione S-transferase theta 1-1 variants.
  Eur J Biochem, 268, 4001-4010.  
11327815 G.Polekhina, P.G.Board, A.C.Blackburn, and M.W.Parker (2001).
Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity.
  Biochemistry, 40, 1567-1576.
PDB code: 1fw1
11533048 M.Lo Bello, M.Nuccetelli, A.M.Caccuri, L.Stella, M.W.Parker, J.Rossjohn, W.J.McKinstry, A.F.Mozzi, G.Federici, F.Polizio, J.Z.Pedersen, and G.Ricci (2001).
Human glutathione transferase P1-1 and nitric oxide carriers; a new role for an old enzyme.
  J Biol Chem, 276, 42138-42145.  
11171973 T.C.Umland, K.L.Taylor, S.Rhee, R.B.Wickner, and D.R.Davies (2001).
The crystal structure of the nitrogen regulation fragment of the yeast prion protein Ure2p.
  Proc Natl Acad Sci U S A, 98, 1459-1464.
PDB code: 1hqo
10737945 J.U.Flanagan, W.King, M.W.Parker, P.G.Board, and G.Chelvanayagam (2000).
Ab initio calculations on hidden modulators of theta class glutathione transferase activity.
  Proteins, 39, 235-243.  
10722701 P.Jemth, and B.Mannervik (2000).
Active site serine promotes stabilization of the reactive glutathione thiolate in rat glutathione transferase T2-2. Evidence against proposed sulfatase activity of the corresponding human enzyme.
  J Biol Chem, 275, 8618-8624.  
10858281 S.A.McCallum, T.K.Hitchens, C.Torborg, and G.S.Rule (2000).
Ligand-induced changes in the structure and dynamics of a human class Mu glutathione S-transferase.
  Biochemistry, 39, 7343-7356.  
11018744 S.Landi (2000).
Mammalian class theta GST and differential susceptibility to carcinogens: a review.
  Mutat Res, 463, 247-283.  
10652317 Y.V.Patskovsky, L.N.Patskovska, and I.Listowsky (2000).
The enhanced affinity for thiolate anion and activation of enzyme-bound glutathione is governed by an arginine residue of human Mu class glutathione S-transferases.
  J Biol Chem, 275, 3296-3304.
PDB code: 2gtu
10587450 A.Gustafsson, M.Etahadieh, P.Jemth, and B.Mannervik (1999).
The C-terminal region of human glutathione transferase A1-1 affects the rate of glutathione binding and the ionization of the active-site Tyr9.
  Biochemistry, 38, 16268-16275.  
10573129 B.Masquida, C.Sauter, and E.Westhof (1999).
A sulfate pocket formed by three GoU pairs in the 0.97 A resolution X-ray structure of a nonameric RNA.
  RNA, 5, 1384-1395.
PDB code: 485d
  10548067 J.U.Flanagan, J.Rossjohn, M.W.Parker, P.G.Board, and G.Chelvanayagam (1999).
Mutagenic analysis of conserved arginine residues in and around the novel sulfate binding pocket of the human Theta class glutathione transferase T2-2.
  Protein Sci, 8, 2205-2212.  
  10631982 S.Ware, J.P.Donahue, J.Hawiger, and W.F.Anderson (1999).
Structure of the fibrinogen gamma-chain integrin binding and factor XIIIa cross-linking sites obtained through carrier protein driven crystallization.
  Protein Sci, 8, 2663-2671.
PDB code: 1dug
9829702 J.U.Flanagan, J.Rossjohn, M.W.Parker, P.G.Board, and G.Chelvanayagam (1998).
A homology model for the human theta-class glutathione transferase T1-1.
  Proteins, 33, 444-454.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.