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PDBsum entry 20gs

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protein ligands Protein-protein interface(s) links
Transferase PDB id
20gs
Jmol
Contents
Protein chain
208 a.a. *
Ligands
MES ×2
CBD ×2
Waters ×101
* Residue conservation analysis
PDB id:
20gs
Name: Transferase
Title: Glutathione s-transferase p1-1 complexed with cibacron blue
Structure: Glutathione s-transferase. Chain: a, b. Synonym: gstp1-1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: ubiquitous. Tissue: ubiquitous. Cell: ubiquitous. Cellular_location: cytosol. Gene: gstp1. Expressed in: escherichia coli.
Biol. unit: Dimer (from PDB file)
Resolution:
2.45Å     R-factor:   0.229     R-free:   0.280
Authors: A.J.Oakley,M.Lo Bello,M.Nuccetelli,A.P.Mazzetti,M.W.Parker
Key ref:
A.J.Oakley et al. (1999). The ligandin (non-substrate) binding site of human Pi class glutathione transferase is located in the electrophile binding site (H-site). J Mol Biol, 291, 913-926. PubMed id: 10452896 DOI: 10.1006/jmbi.1999.3029
Date:
16-Dec-97     Release date:   30-Dec-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P09211  (GSTP1_HUMAN) -  Glutathione S-transferase P
Seq:
Struc:
210 a.a.
208 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
= 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     TRAF2-GSTP1 complex   9 terms 
  Biological process     metabolic process   31 terms 
  Biochemical function     S-nitrosoglutathione binding     8 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.1999.3029 J Mol Biol 291:913-926 (1999)
PubMed id: 10452896  
 
 
The ligandin (non-substrate) binding site of human Pi class glutathione transferase is located in the electrophile binding site (H-site).
A.J.Oakley, M.Lo Bello, M.Nuccetelli, A.P.Mazzetti, M.W.Parker.
 
  ABSTRACT  
 
Glutathione S -transferases (GSTs) play a pivotal role in the detoxification of foreign chemicals and toxic metabolites. They were originally termed ligandins because of their ability to bind large molecules (molecular masses >400 Da), possibly for storage and transport roles. The location of the ligandin site in mammalian GSTs is still uncertain despite numerous studies in recent years. Here we show by X-ray crystallography that the ligandin binding site in human pi class GST P1-1 occupies part of one of the substrate binding sites. This work has been extended to the determination of a number of enzyme complex crystal structures which show that very large ligands are readily accommodated into this substrate binding site and in all, but one case, causes no significant movement of protein side-chains. Some of these molecules make use of a hitherto undescribed binding site located in a surface pocket of the enzyme. This site is conserved in most, but not all, classes of GSTs suggesting it may play an important functional role.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Schematic representation of the inhibitors. (a) Sulfasalazine. The numbering scheme is taken from [van der Sluis and Spek 1990]. (b) S-Nonyl GSH; (c) Cibacron blue; (d) bromosulfophthalein; (e) 2,4-dinitrophenyl GSH.
Figure 3.
Figure 3. A comparison of the binding locations of GSH conjugates derived from the various crystal structures of pi class GSTs presented here. The superposition was based on overlaying the coordinates of the respective N-terminal domains. The ligands are overlayed on a schematic of the N-terminal domain of the human pi class enzyme. (a) Stereo view showing all inhibitors described in the text. The inhibitors are coloured as follows: SLZ, yellow;S-nonyl GSH, cyan; CB, dark blue; BS no.1, red; BS no. 2, magenta; DNP GSH, green. The side-chains of Phe8 and Tyr108 are shown. (b) Comparison of the binding locations of DNP GSH (denoted by yellow bonds) and BS no. 1 (denoted by red bonds). These pictures were generated with the program MOLSCRIPT [Kraulis 1991].
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 291, 913-926) copyright 1999.  
  Figures were 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.  
  21428694 F.Morel, and C.Aninat (2011).
The glutathione transferase kappa family.
  Drug Metab Rev, 43, 281-291.  
  21425928 J.U.Flanagan, and M.L.Smythe (2011).
Sigma-class glutathione transferases.
  Drug Metab Rev, 43, 194-214.  
20823552 F.Pavelcík, and J.Václavík (2010).
Performance of phased rotation, conformation and translation function: accurate protein model building with tripeptidic and tetrapeptidic fragments.
  Acta Crystallogr D Biol Crystallogr, 66, 1012-1023.  
  19052367 E.H.Jang, H.Park, A.K.Park, J.H.Moon, Y.M.Chi, and I.Y.Ahn (2008).
Crystallization and preliminary X-ray crystallographic studies of the rho-class glutathione S-transferase from the Antarctic clam Laternula elliptica.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1132-1134.  
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.  
18691867 P.Kapoli, I.A.Axarli, D.Platis, M.Fragoulaki, M.Paine, J.Hemingway, J.Vontas, and N.E.Labrou (2008).
Engineering sensitive glutathione transferase for the detection of xenobiotics.
  Biosens Bioelectron, 24, 498-503.  
18836188 S.Conn, C.Curtin, A.Bézier, C.Franco, and W.Zhang (2008).
Purification, molecular cloning, and characterization of glutathione S-transferases (GSTs) from pigmented Vitis vinifera L. cell suspension cultures as putative anthocyanin transport proteins.
  J Exp Bot, 59, 3621-3634.  
15757902 H.W.Dirr, T.Little, D.C.Kuhnert, and Y.Sayed (2005).
A conserved N-capping motif contributes significantly to the stabilization and dynamics of the C-terminal region of class Alpha glutathione S-transferases.
  J Biol Chem, 280, 19480-19487.  
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
14742434 F.Morel, C.Rauch, E.Petit, A.Piton, N.Theret, B.Coles, and A.Guillouzo (2004).
Gene and protein characterization of the human glutathione S-transferase kappa and evidence for a peroxisomal localization.
  J Biol Chem, 279, 16246-16253.  
  18185852 M.H.Hanigan, and P.Devarajan (2003).
Cisplatin nephrotoxicity: molecular mechanisms.
  Cancer Ther, 1, 47-61.  
14690442 S.Mosebi, Y.Sayed, J.Burke, and H.W.Dirr (2003).
Residue 219 impacts on the dynamics of the C-terminal region in glutathione transferase A1-1: implications for stability and catalytic and ligandin functions.
  Biochemistry, 42, 15326-15332.  
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
11123923 C.Micaloni, A.P.Mazzetti, M.Nuccetelli, J.Rossjohn, W.J.McKinstry, G.Antonini, A.M.Caccuri, A.J.Oakley, G.Federici, G.Ricci, M.W.Parker, and M.Lo Bello (2000).
Valine 10 may act as a driver for product release from the active site of human glutathione transferase P1-1.
  Biochemistry, 39, 15961-15970.  
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.