PDBsum entry 1hna

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Transferase(glutathione) PDB id
Protein chain
217 a.a. *
Waters ×108
* Residue conservation analysis
PDB id:
Name: Transferase(glutathione)
Title: Crystal structure of human class mu glutathione transferase gstm2-2: effects of lattice packing on conformational heterogeneity
Structure: Glutathione s-transferase. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Biol. unit: Dimer (from PQS)
1.85Å     R-factor:   0.226    
Authors: S.Raghunathan,R.J.Chandross,R.H.Kretsinger,T.J.Allison, C.J.Penington,G.S.Rule
Key ref: S.Raghunathan et al. (1994). Crystal structure of human class mu glutathione transferase GSTM2-2. Effects of lattice packing on conformational heterogeneity. J Mol Biol, 238, 815-832. PubMed id: 8182750
15-Oct-93     Release date:   31-Jan-94    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P28161  (GSTM2_HUMAN) -  Glutathione S-transferase Mu 2
218 a.a.
217 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
Bound ligand (Het Group name = GDN)
corresponds exactly
= 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     metabolic process   15 terms 
  Biochemical function     transferase activity     6 terms  


J Mol Biol 238:815-832 (1994)
PubMed id: 8182750  
Crystal structure of human class mu glutathione transferase GSTM2-2. Effects of lattice packing on conformational heterogeneity.
S.Raghunathan, R.J.Chandross, R.H.Kretsinger, T.J.Allison, C.J.Penington, G.S.Rule.
The structures of three crystal forms of the class mu human glutathione transferase GSTM2-2 have been determined. X-ray phase information was obtained independently from molecular replacement and from anomalous scattering by a single isomorphous derivative. One crystal form contains a single monomer in the asymmetric unit and has been refined to 1.85 A with an overall R factor of 22.6%. The second form contains a single dimer in the asymmetric unit and has been refined to 3.5 A with an R factor of 20.7%. The third form contains two dimers in the asymmetric unit and has been refined to 3.0 A with an R factor of 25.0%. Although all three crystal forms were grown from solutions that contained glutathione-dinitrobenzene, electron density can only be seen for the glutathione portion of the ligand. The first 202 residues in the seven crystallographically independent monomers of GSTM2-2 are essentially identical in structure. However, heterogeneity in the conformation of the side-chain of Tyr115 is observed in the different monomers. The tertiary structure of residues 1-202 is similar to that of the corresponding region in the class mu isoform of glutathione transferase from rat, GST3-3 (Ji et al. (1992), Biochemistry, 31, 10169-10184). However, significant differences in the conformation of the two enzymes have been observed in the region of the active site that binds hydrophobic substrates. These differences include a 2 A shift in the carboxy terminus of a helix, and significant heterogeneity in the conformation of the last 15 residues of the carboxy terminus. The conformation and degree of disorder of the last 15 residues correlates with the extent of protein-protein contacts within the unit cell.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21323602 A.F.Dulhunty, R.Hewawasam, D.Liu, M.G.Casarotto, and P.G.Board (2011).
Regulation of the cardiac muscle ryanodine receptor by glutathione transferases.
  Drug Metab Rev, 43, 236-252.  
18792041 D.F.Dourado, P.A.Fernandes, B.Mannervik, and M.J.Ramos (2008).
Glutathione transferase: new model for glutathione activation.
  Chemistry, 14, 9591-9598.  
17682821 B.Blanchette, X.Feng, and B.R.Singh (2007).
Marine glutathione S-transferases.
  Mar Biotechnol (NY), 9, 513-542.  
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
16154081 F.Angelucci, P.Baiocco, M.Brunori, L.Gourlay, V.Morea, and A.Bellelli (2005).
Insights into the catalytic mechanism of glutathione S-transferase: the lesson from Schistosoma haematobium.
  Structure, 13, 1241-1246.  
12972411 M.Perbandt, C.Burmeister, R.D.Walter, C.Betzel, and E.Liebau (2004).
Native and inhibited structure of a Mu class-related glutathione S-transferase from Plasmodium falciparum.
  J Biol Chem, 279, 1336-1342.
PDB codes: 1pa3 1q4j
15247628 N.Tetlow, A.Robinson, T.Mantle, and P.Board (2004).
Polymorphism of human mu class glutathione transferases.
  Pharmacogenetics, 14, 359-368.  
12596270 R.M.Cardoso, D.S.Daniels, C.M.Bruns, and J.A.Tainer (2003).
Characterization of the electrophile binding site and substrate binding mode of the 26-kDa glutathione S-transferase from Schistosoma japonicum.
  Proteins, 51, 137-146.
PDB codes: 1m99 1m9a 1m9b
12486119 Y.Ivarsson, A.J.Mackey, M.Edalat, W.R.Pearson, and B.Mannervik (2003).
Identification of residues in glutathione transferase capable of driving functional diversification in evolution. A novel approach to protein redesign.
  J Biol Chem, 278, 8733-8738.  
11889135 A.M.Caccuri, G.Antonini, N.Allocati, C.Di Ilio, F.De Maria, F.Innocenti, M.W.Parker, M.Masulli, M.Lo Bello, P.Turella, G.Federici, and G.Ricci (2002).
GSTB1-1 from Proteus mirabilis: a snapshot of an enzyme in the evolutionary pathway from a redox enzyme to a conjugating enzyme.
  J Biol Chem, 277, 18777-18784.  
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
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.  
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
  10631991 L.O.Hansson, R.Bolton-Grob, M.Widersten, and B.Mannervik (1999).
Structural determinants in domain II of human glutathione transferase M2-2 govern the characteristic activities with aminochrome, 2-cyano-1,3-dimethyl-1-nitrosoguanidine, and 1,2-dichloro-4-nitrobenzene.
  Protein Sci, 8, 2742-2750.  
9930979 Y.V.Patskovsky, L.N.Patskovska, and I.Listowsky (1999).
Functions of His107 in the catalytic mechanism of human glutathione S-transferase hGSTM1a-1a.
  Biochemistry, 38, 1193-1202.
PDB code: 1gtu
9761928 L.N.Patskovska, A.A.Fedorov, Y.V.Patskovsky, S.C.Almo, and I.Listowsky (1998).
Expression, crystallization and preliminary X-ray analysis of ligand-free human glutathione S-transferase M2-2.
  Acta Crystallogr D Biol Crystallogr, 54, 458-460.  
9446594 M.C.Vega, S.B.Walsh, T.J.Mantle, and M.Coll (1998).
The three-dimensional structure of Cys-47-modified mouse liver glutathione S-transferase P1-1. Carboxymethylation dramatically decreases the affinity for glutathione and is associated with a loss of electron density in the alphaB-310B region.
  J Biol Chem, 273, 2844-2850.
PDB codes: 1bay 1gti
9485454 M.Nicotra, M.Paci, M.Sette, A.J.Oakley, M.W.Parker, M.Lo Bello, A.M.Caccuri, G.Federici, and G.Ricci (1998).
Solution structure of glutathione bound to human glutathione transferase P1-1: comparison of NMR measurements with the crystal structure.
  Biochemistry, 37, 3020-3027.  
9761841 W.J.McKinstry, A.J.Oakley, J.Rossjohn, D.Verger, K.L.Tan, P.G.Board, and M.W.Parker (1998).
Preliminary X-ray crystallographic studies of a newly defined human theta-class glutathione transferase.
  Acta Crystallogr D Biol Crystallogr, 54, 148-150.  
9037717 G.Chelvanayagam, M.C.Wilce, M.W.Parker, K.L.Tan, and P.G.Board (1997).
Homology model for the human GSTT2 Theta class glutathione transferase.
  Proteins, 27, 118-130.  
9287168 L.O.Hansson, M.Widersten, and B.Mannervik (1997).
Mechanism-based phage display selection of active-site mutants of human glutathione transferase A1-1 catalyzing SNAr reactions.
  Biochemistry, 36, 11252-11260.  
  9260294 M.Kuge, Y.Fujii, T.Shimizu, F.Hirose, A.Matsukage, and T.Hakoshima (1997).
Use of a fusion protein to obtain crystals suitable for X-ray analysis: crystallization of a GST-fused protein containing the DNA-binding domain of DNA replication-related element-binding factor, DREF.
  Protein Sci, 6, 1783-1786.  
9188738 R.T.Koehler, H.O.Villar, K.E.Bauer, and D.L.Higgins (1997).
Ligand-based protein alignment and isozyme specificity of glutathione S-transferase inhibitors.
  Proteins, 28, 202-216.  
9245401 X.Ji, M.Tordova, R.O'Donnell, J.F.Parsons, J.B.Hayden, G.L.Gilliland, and P.Zimniak (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.
PDB codes: 1pgt 2pgt
  8762135 J.Wang, J.J.Barycki, and R.F.Colman (1996).
Tyrosine 8 contributes to catalysis but is not required for activity of rat liver glutathione S-transferase, 1-1.
  Protein Sci, 5, 1032-1042.  
8672473 M.Widersten, R.Björnestedt, and B.Mannervik (1996).
Involvement of the carboxyl groups of glutathione in the catalytic mechanism of human glutathione transferase A1-1.
  Biochemistry, 35, 7731-7742.  
8917446 N.Sluis-Cremer, N.N.Naidoo, W.H.Kaplan, T.H.Manoharan, W.E.Fahl, and H.W.Dirr (1996).
Determination of a binding site for a non-substrate ligand in mammalian cytosolic glutathione S-transferases by means of fluorescence-resonance energy transfer.
  Eur J Biochem, 241, 484-488.  
8694853 R.Whalen, E.S.Kempner, and T.D.Boyer (1996).
Structural studies of a human pi class glutathione S-transferase. Photoaffinity labeling of the active site and target size analysis.
  Biochem Pharmacol, 52, 281-288.  
8710848 X.Ji, E.C.von Rosenvinge, W.W.Johnson, R.N.Armstrong, and G.L.Gilliland (1996).
Location of a potential transport binding site in a sigma class glutathione transferase by x-ray crystallography.
  Proc Natl Acad Sci U S A, 93, 8208-8213.
PDB code: 2gsq
8591048 A.D.Cameron, I.Sinning, G.L'Hermite, B.Olin, P.G.Board, B.Mannervik, and T.A.Jones (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.
PDB codes: 1gsd 1gse 1gsf
7667397 A.M.Gulick, and W.E.Fahl (1995).
Mammalian glutathione S-transferase: regulation of an enzyme system to achieve chemotherapeutic efficacy.
  Pharmacol Ther, 66, 237-257.  
8789194 C.S.Poornima, and P.M.Dean (1995).
Hydration in drug design. 3. Conserved water molecules at the ligand-binding sites of homologous proteins.
  J Comput Aided Mol Des, 9, 521-531.  
7814427 H.C.Lee, Y.P.Toung, Y.S.Tu, and C.P.Tu (1995).
A molecular genetic approach for the identification of essential residues in human glutathione S-transferase function in Escherichia coli.
  J Biol Chem, 270, 99.  
7607236 J.Erhardt, and H.Dirr (1995).
Native dimer stabilizes the subunit tertiary structure of porcine class pi glutathione S-transferase.
  Eur J Biochem, 230, 614-620.  
7675787 M.A.McTigue, S.L.Bernstein, D.R.Williams, and J.A.Tainer (1995).
Purification and crystallization of a schistosomal glutathione S-transferase.
  Proteins, 22, 55-57.  
  7774571 M.C.Wilce, P.G.Board, S.C.Feil, and M.W.Parker (1995).
Crystal structure of a theta-class glutathione transferase.
  EMBO J, 14, 2133-2143.  
8530359 R.Björnestedt, S.Tardioli, and B.Mannervik (1995).
The high activity of rat glutathione transferase 8-8 with alkene substrates is dependent on a glycine residue in the active site.
  J Biol Chem, 270, 29705-29709.  
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.