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PDBsum entry 5fwg

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protein ligands Protein-protein interface(s) links
Transferase PDB id
5fwg
Jmol
Contents
Protein chains
217 a.a. *
Ligands
GPR ×2
Waters ×371
* Residue conservation analysis
PDB id:
5fwg
Name: Transferase
Title: Tetra-(5-fluorotryptophanyl)-glutathione transferase
Structure: Tetra-(5-fluorotryptophanyl)-glutathione transferase mu class. Chain: a, b. Synonym: rat mu class gst, rat m1-1 gst. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Cell_line: bl21. Organ: liver. Gene: cdna insert of 3-3 (m1-1) enzy. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
Resolution:
2.00Å     R-factor:   0.180    
Authors: J.F.Parsons,G.Xiao,R.N.Armstrong,G.L.Gilliland
Key ref:
X.Ji et al. (1994). Structure and function of the xenobiotic substrate binding site of a glutathione S-transferase as revealed by X-ray crystallographic analysis of product complexes with the diastereomers of 9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene. Biochemistry, 33, 1043-1052. PubMed id: 8110735 DOI: 10.1021/bi00171a002
Date:
08-Nov-97     Release date:   27-Jan-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04905  (GSTM1_RAT) -  Glutathione S-transferase Mu 1
Seq:
Struc:
218 a.a.
217 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 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 = GPR)
matches with 57.00% 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     extracellular region   3 terms 
  Biological process     metabolic process   12 terms 
  Biochemical function     transferase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi00171a002 Biochemistry 33:1043-1052 (1994)
PubMed id: 8110735  
 
 
Structure and function of the xenobiotic substrate binding site of a glutathione S-transferase as revealed by X-ray crystallographic analysis of product complexes with the diastereomers of 9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene.
X.Ji, W.W.Johnson, M.A.Sesay, L.Dickert, S.M.Prasad, H.L.Ammon, R.N.Armstrong, G.L.Gilliland.
 
  ABSTRACT  
 
The three-dimensional structures of isoenzyme 3-3 of glutathione (GSH) transferase complexed with (9R,10R)- and (9S,10S)-9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene [(9R,10R)-2 and (9S,10S)-2], which are the products of the addition of GSH to phenanthrene 9,10-oxide, have been determined at resolutions of 1.9 and 1.8 A, respectively. The structures indicate that the xenobiotic substrate binding site is a hydrophobic cavity defined by the side chains of Y6, W7, V9, and L12 from domain I (the GSH binding domain) and I111, Y115, F208, and S209 in domain II of the protein. All of these residues are located in variable-sequence regions of the primary structure of class mu isoenzymes. Three of the eight residues (V9, I111, and S209) of isoenzyme 3-3 that are in direct van der Waals contact with the dihydrophenanthrenyl portion of the products are mutated (V9I, I111A, and S209A) in the related isoenzyme 4-4. These three residues are implicated in control of the stereoselectivity of the class mu isoenzymes. The hydroxyl group of Y115 is found to be hydrogen-bonded to the 10-hydroxyl group of (9S,10S)-2, a fact suggesting that this residue could act as an electrophile to stabilize the transition state for the addition of GSH to epoxides. The Y115F mutant isoenzyme 3-3 is about 100-fold less efficient than the native enzyme in catalyzing the addition of GSH to phenanthrene 9,10-oxide and about 50-fold less efficient in the Michael addition of GSH to 4-phenyl-3-buten-2-one. The side chain of Y115 is positioned so as to act as a general-acid catalytic group for two types of reactions that would benefit from electrophilic assistance. The results are consistent with the notion that domain II, which harbors most of the variability in primary structure, plays a crucial role in defining the substrate specificity of class mu isoenzymes.
 

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.  
  21495793 L.G.Higgins, and J.D.Hayes (2011).
Mechanisms of induction of cytosolic and microsomal glutathione transferase (GST) genes by xenobiotics and pro-inflammatory agents.
  Drug Metab Rev, 43, 92.  
20196771 J.Wongsantichon, R.C.Robinson, and A.J.Ketterman (2010).
Structural contributions of delta class glutathione transferase active-site residues to catalysis.
  Biochem J, 428, 25-32.
PDB codes: 3f63 3f6d 3g7j
18703268 N.Kinsley, Y.Sayed, S.Mosebi, R.N.Armstrong, and H.W.Dirr (2008).
Characterization of the binding of 8-anilinonaphthalene sulfonate to rat class Mu GST M1-1.
  Biophys Chem, 137, 100-104.  
  19662104 X.Ji, A.Pal, R.Kalathur, X.Hu, Y.Gu, J.E.Saavedra, G.S.Buzard, A.Srinivasan, L.K.Keefer, and S.V.Singh (2008).
Structure-Based Design of Anticancer Prodrug PABA/NO.
  Drug Des Devel Ther, 2, 123-130.  
17915350 G.Cornilescu, E.B.Hadley, M.G.Woll, J.L.Markley, S.H.Gellman, and C.C.Cornilescu (2007).
Solution structure of a small protein containing a fluorinated side chain in the core.
  Protein Sci, 16, 2089.  
16672236 J.L.Hearne, and R.F.Colman (2006).
Contribution of the mu loop to the structure and function of rat glutathione transferase M1-1.
  Protein Sci, 15, 1277-1289.  
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
15549710 C.A.Contreras-Vergara, C.Harris-Valle, R.R.Sotelo-Mundo, and G.Yepiz-Plascencia (2004).
A mu-class glutathione S-transferase from the marine shrimp Litopenaeus vannamei: molecular cloning and active-site structural modeling.
  J Biochem Mol Toxicol, 18, 245-252.  
15146492 C.DeWeese-Scott, and J.Moult (2004).
Molecular modeling of protein function regions.
  Proteins, 55, 942-961.  
15347687 L.A.Ralat, and R.F.Colman (2004).
Glutathione S-transferase Pi has at least three distinguishable xenobiotic substrate sites close to its glutathione-binding site.
  J Biol Chem, 279, 50204-50213.  
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.  
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
11027134 Y.Gu, S.V.Singh, and X.Ji (2000).
Residue R216 and catalytic efficiency of a murine class alpha glutathione S-transferase toward benzo[a]pyrene 7(R),8(S)-diol 9(S), 10(R)-epoxide.
  Biochemistry, 39, 12552-12557.
PDB codes: 1f3a 1f3b
9572843 J.F.Parsons, G.Xiao, G.L.Gilliland, and R.N.Armstrong (1998).
Enzymes harboring unnatural amino acids: mechanistic and structural analysis of the enhanced catalytic activity of a glutathione transferase containing 5-fluorotryptophan.
  Biochemistry, 37, 6286-6294.
PDB code: 5fwg
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.  
  9007975 L.Hu, B.L.Borleske, and R.F.Colman (1997).
Probing the active site of alpha-class rat liver glutathione S-transferases using affinity labeling by monobromobimane.
  Protein Sci, 6, 43-52.  
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
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
  8762136 K.K.Koretke, Z.Luthey-Schulten, and P.G.Wolynes (1996).
Self-consistently optimized statistical mechanical energy functions for sequence structure alignment.
  Protein Sci, 5, 1043-1059.  
8654388 S.I.Tomarev, and J.Piatigorsky (1996).
Lens crystallins of invertebrates--diversity and recruitment from detoxification enzymes and novel proteins.
  Eur J Biochem, 235, 449-465.  
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.  
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
7667259 A.M.Gulick, and W.E.Fahl (1995).
Forced evolution of glutathione S-transferase to create a more efficient drug detoxication enzyme.
  Proc Natl Acad Sci U S A, 92, 8140-8144.  
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.  
  8770536 J.D.Hayes, and D.J.Pulford (1995).
The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.
  Crit Rev Biochem Mol Biol, 30, 445-600.  
7665611 L.Hu, and R.F.Colman (1995).
Monobromobimane as an affinity label of the xenobiotic binding site of rat glutathione S-transferase 3-3.
  J Biol Chem, 270, 21875-21883.  
  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.  
  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
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 codes are shown on the right.