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PDBsum entry 1glq

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protein ligands Protein-protein interface(s) links
Transferase(glutathione) PDB id
1glq
Jmol
Contents
Protein chains
209 a.a. *
Ligands
GTB ×2
Waters ×148
* Residue conservation analysis
PDB id:
1glq
Name: Transferase(glutathione)
Title: 1.8 angstroms molecular structure of mouse liver class pi glutathione s-transferase complexed with s-(p-nitrobenzyl) glutathione and other inhibitors
Structure: Glutathione s-transferase yfyf. Chain: a, b. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090
Biol. unit: Dimer (from PQS)
Resolution:
1.80Å     R-factor:   0.185    
Authors: I.Garcia-Saez,M.Coll
Key ref: I.García-Sáez et al. (1994). Molecular structure at 1.8 A of mouse liver class pi glutathione S-transferase complexed with S-(p-nitrobenzyl)glutathione and other inhibitors. J Mol Biol, 237, 298-314. PubMed id: 8145243
Date:
07-Mar-94     Release date:   31-May-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P19157  (GSTP1_MOUSE) -  Glutathione S-transferase P 1
Seq:
Struc:
210 a.a.
209 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.5.1.18  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
RX
+
glutathione
Bound ligand (Het Group name = GTB)
matches with 66.00% similarity
= 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     protein complex   7 terms 
  Biological process     metabolic process   38 terms 
  Biochemical function     drug binding     5 terms  

 

 
    reference    
 
 
J Mol Biol 237:298-314 (1994)
PubMed id: 8145243  
 
 
Molecular structure at 1.8 A of mouse liver class pi glutathione S-transferase complexed with S-(p-nitrobenzyl)glutathione and other inhibitors.
I.García-Sáez, A.Párraga, M.F.Phillips, T.J.Mantle, M.Coll.
 
  ABSTRACT  
 
The three-dimensional crystal structure of pi class glutathione S-transferase YfYf from mouse liver complexed with the inhibitor S-(p-nitrobenzyl)glutathione has been determined at 1.8 A resolution by X-ray diffraction. In addition two complexes with glutathione sulphonic acid and S-hexylglutathione have been determined at resolutions of 1.9 and 2.2 A, respectively. The high resolution of the S-(p-nitrobenzyl)glutathione complex allows a detailed analysis of the active site including the hydrophobic (H-) subsite. The nitrobenzyl moiety occupies a hydrophobic pocket with its aromatic ring sandwiched between Phe8 and the hydroxyl group of Tyr108. An insertion of two residues Gly41 and Leu42, with respect to the pig enzyme, splits helix alpha B into an alpha-helix and a 3(10) helix. Water bridges between carbonyl oxygen atoms of the alpha-helix at its C terminus and the amide NH groups of the 3(10) helix at its N terminus provide structural continuity between these two secondary elements. Tyr7 appears to be the only residue close to the sulphur atom of glutathione, while three conserved water molecules lie in the surrounding area in all complexes. The enzyme mechanism is discussed on the basis of the structural analysis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21134126 G.McManus, M.Costa, A.Canals, M.Coll, and T.J.Mantle (2011).
Site-directed mutagenesis of mouse glutathione transferase P1-1 unlocks masked cooperativity, introduces a novel mechanism for 'ping pong' kinetic behaviour, and provides further structural evidence for participation of a water molecule in proton abstraction from glutathione.
  FEBS J, 278, 273-281.
PDB code: 3o76
20526737 S.Lu, Z.Wang, D.Cui, H.Liu, and X.Hao (2011).
Glutathione S-transferase P1 Ile105Val polymorphism and breast cancer risk: a meta-analysis involving 34,658 subjects.
  Breast Cancer Res Treat, 125, 253-259.  
  20205309 X.F.Tan, F.Chen, S.S.Wu, Y.Shi, D.C.Liu, and Z.Chen (2010).
Science letters: Proteomic analysis of differentially expressed proteins in mice with concanavalin A-induced hepatitis.
  J Zhejiang Univ Sci B, 11, 221-226.  
18521819 A.Unlü, N.A.Ates, L.Tamer, and C.Ates (2008).
Relation of glutathione S-transferase T1, M1 and P1 genotypes and breast cancer risk.
  Cell Biochem Funct, 26, 643-647.  
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
15640152 M.Perbandt, J.Höppner, C.Betzel, R.D.Walter, and E.Liebau (2005).
Structure of the major cytosolic glutathione S-transferase from the parasitic nematode Onchocerca volvulus.
  J Biol Chem, 280, 12630-12636.
PDB codes: 1tu7 1tu8
14676193 U.M.Hegazy, B.Mannervik, and G.Stenberg (2004).
Functional role of the lock and key motif at the subunit interface of glutathione transferase p1-1.
  J Biol Chem, 279, 9586-9596.  
12565703 A.Pennelli, P.Sacchetta, C.Catitti, F.Amicarelli, and C.Di Ilio (2003).
Effects of glutathione on kinetics and structural properties of amphibian BbGSTP1-1.
  Int J Biochem Cell Biol, 35, 415-421.  
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
11276081 D.J.Diller, and K.M.Merz (2001).
High throughput docking for library design and library prioritization.
  Proteins, 43, 113-124.  
11470996 P.Piirilä, H.Wikman, R.Luukkonen, K.Kääriä, C.Rosenberg, H.Nordman, H.Norppa, H.Vainio, and A.Hirvonen (2001).
Glutathione S-transferase genotypes and allergic responses to diisocyanate exposure.
  Pharmacogenetics, 11, 437-445.  
10559245 L.Tang, B.Guo, A.Javed, J.Y.Choi, S.Hiebert, J.B.Lian, A.J.van Wijnen, J.L.Stein, G.S.Stein, and G.W.Zhou (1999).
Crystal structure of the nuclear matrix targeting signal of the transcription factor acute myelogenous leukemia-1/polyoma enhancer-binding protein 2alphaB/core binding factor alpha2.
  J Biol Chem, 274, 33580-33586.  
9665696 A.J.Oakley, M.Lo Bello, G.Ricci, G.Federici, and M.W.Parker (1998).
Evidence for an induced-fit mechanism operating in pi class glutathione transferases.
  Biochemistry, 37, 9912-9917.
PDB codes: 14gs 16gs
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
9761122 S.Morita, M.Yano, T.Tsujinaka, A.Ogawa, M.Taniguchi, K.Kaneko, H.Shiozaki, Y.Doki, M.Inoue, and M.Monden (1998).
Association between genetic polymorphisms of glutathione S-transferase P1 and N-acetyltransferase 2 and susceptibility to squamous-cell carcinoma of the esophagus.
  Int J Cancer, 79, 517-520.  
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.  
9012673 A.J.Oakley, J.Rossjohn, M.Lo Bello, A.M.Caccuri, G.Federici, and M.W.Parker (1997).
The three-dimensional structure of the human Pi class glutathione transferase P1-1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate.
  Biochemistry, 36, 576-585.
PDB codes: 2gss 3gss
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.  
9351803 L.Prade, R.Huber, T.H.Manoharan, W.E.Fahl, and W.Reuter (1997).
Structures of class pi glutathione S-transferase from human placenta in complex with substrate, transition-state analogue and inhibitor.
  Structure, 5, 1287-1295.
PDB codes: 1aqv 1aqw 1aqx
  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.  
9166793 M.Lo Bello, A.J.Oakley, A.Battistoni, A.P.Mazzetti, M.Nuccetelli, G.Mazzarese, J.Rossjohn, M.W.Parker, and G.Ricci (1997).
Multifunctional role of Tyr 108 in the catalytic mechanism of human glutathione transferase P1-1. Crystallographic and kinetic studies on the Y108F mutant enzyme.
  Biochemistry, 36, 6207-6217.
PDB code: 4gss
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
8810897 E.C.Dietze, C.Ibarra, M.J.Dabrowski, A.Bird, and W.M.Atkins (1996).
Rational modulation of the catalytic activity of A1-1 glutathione S-transferase: evidence for incorporation of an on-face (pi...HO-Ar) hydrogen bond at tyrosine-9.
  Biochemistry, 35, 11938-11944.  
8664265 G.Xiao, S.Liu, X.Ji, W.W.Johnson, J.Chen, J.F.Parsons, W.J.Stevens, G.L.Gilliland, and R.N.Armstrong (1996).
First-sphere and second-sphere electrostatic effects in the active site of a class mu gluthathione transferase.
  Biochemistry, 35, 4753-4765.
PDB codes: 6gst 6gsu 6gsv 6gsw 6gsx 6gsy
8694843 J.P.Ploemen, M.L.van Iersel, L.W.Wormhoudt, J.N.Commandeur, N.P.Vermeulen, and P.J.van Bladeren (1996).
In vitro inhibition of rat and human glutathione S-transferase isoenzymes by disulfiram and diethyldithiocarbamate.
  Biochem Pharmacol, 52, 197-204.  
8702779 J.Zheng, A.E.Mitchell, A.D.Jones, and B.D.Hammock (1996).
Haloenol lactone is a new isozyme-selective and active site-directed inactivator of glutathione S-transferase.
  J Biol Chem, 271, 20421-20425.  
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.  
8973647 N.Sluis-Cremer, N.Naidoo, and H.Dirr (1996).
Class-pi glutathione S-transferase is unable to regain its native conformation after oxidative inactivation by hydrogen peroxide.
  Eur J Biochem, 242, 301-307.  
8910329 T.E.McHugh, W.M.Atkins, J.K.Racha, K.L.Kunze, and D.L.Eaton (1996).
Binding of the aflatoxin-glutathione conjugate to mouse glutathione S-transferase A3-3 is saturated at only one ligand per dimer.
  J Biol Chem, 271, 27470-27474.  
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.  
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.  
7556138 J.Nishihira, M.Sakai, S.Nishi, and Y.Hatanaka (1995).
Identification of the electrophilic substrate-binding site of glutathione S-transferase P by photoaffinity labeling.
  Eur J Biochem, 232, 106-110.  
  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.  
7696312 P.Bico, J.Erhardt, W.Kaplan, and H.Dirr (1995).
Porcine class pi glutathione S-transferase: anionic ligand binding and conformational analysis.
  Biochim Biophys Acta, 1247, 225-230.  
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.  
  7703850 E.V.Koonin, A.R.Mushegian, R.L.Tatusov, S.F.Altschul, S.H.Bryant, P.Bork, and A.Valencia (1994).
Eukaryotic translation elongation factor 1 gamma contains a glutathione transferase domain--study of a diverse, ancient protein superfamily using motif search and structural modeling.
  Protein Sci, 3, 2045-2054.  
  7538846 K.Lim, J.X.Ho, K.Keeling, G.L.Gilliland, X.Ji, F.Rüker, and D.C.Carter (1994).
Three-dimensional structure of Schistosoma japonicum glutathione S-transferase fused with a six-amino acid conserved neutralizing epitope of gp41 from HIV.
  Protein Sci, 3, 2233-2244.
PDB code: 1gne
7925413 P.Zimniak, B.Nanduri, S.Pikuła, J.Bandorowicz-Pikuła, S.S.Singhal, S.K.Srivastava, S.Awasthi, and Y.C.Awasthi (1994).
Naturally occurring human glutathione S-transferase GSTP1-1 isoforms with isoleucine and valine in position 104 differ in enzymic properties.
  Eur J Biochem, 224, 893-899.  
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.