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PDBsum entry 1f3a

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1f3a
Jmol PyMol
Contents
Protein chains
221 a.a. *
Ligands
GSH ×2
Waters ×450
* Residue conservation analysis
PDB id:
1f3a
Name: Transferase
Title: Crystal structure of mgsta1-1 in complex with gsh
Structure: Glutathione s-transferase ya chain. Chain: a, b. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.191     R-free:   0.248
Authors: Y.Gu,S.V.Singh,X.Ji
Key ref:
Y.Gu et al. (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. PubMed id: 11027134 DOI: 10.1021/bi001396u
Date:
01-Jun-00     Release date:   18-Oct-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P13745  (GSTA1_MOUSE) -  Glutathione S-transferase A1
Seq:
Struc:
223 a.a.
221 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 = GSH)
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     extracellular vesicular exosome   2 terms 
  Biological process     metabolic process   3 terms 
  Biochemical function     transferase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi001396u Biochemistry 39:12552-12557 (2000)
PubMed id: 11027134  
 
 
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.
Y.Gu, S.V.Singh, X.Ji.
 
  ABSTRACT  
 
Murine class alpha glutathione S-transferase A1-1 (mGSTA1-1), unlike mammalian class alpha GSTs, is the most efficient in the glutathione (GSH) conjugation of the ultimate carcinogenic metabolite of benzo[a]pyrene, (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] [Hu, X., Srivastava, S. K., Xia, H., Awasthi, Y. C., and Singh, S. V. (1996) J. Biol. Chem. 271, 32684-32688]. Here, we report the crystal structures of mGSTA1-1 in complex with GSH and with the GSH conjugate of (+)-anti-BPDE (GSBpd) at 1.9 and 2.0 A resolution, respectively. Both crystals belong to monoclinic space group C2 with one dimer in the asymmetric unit. The structures reveal that, within one subunit, the GSH moiety interacts with residues Y8, R14, K44, Q53, V54, Q66, and T67, whereas the hydrophobic moiety of GSBpd interacts with the side chains of F9, R14, M207, A215, R216, F219, and I221. In addition, the GSH moiety interacts with D100 and R130 from the other subunit across the dimer interface. The structural comparison between mGSTA1-1.GSH and mGSTA1-1.GSBpd reveals significant conformational differences. The movement of helix alpha9 brings the residues on the helix into direct interaction with the product. Most noticeable are the positional displacement and conformational change of R216, one of the residues located in helix alpha9. The side chain of R216, which points away from the H-site in the mGSTA1-1.GSH complex, probes into the active site and becomes parallel with the aromatic ring system of GSBpd. Moreover, the guanidinium group of R216 shifts approximately 8 A and forms a strong hydrogen bond with the C8 hydroxyl group of GSBpd, suggesting that the electrostatic assistance provided by the guanidinium group facilitates the ring-opening reaction of (+)-anti-BPDE. The structure of mGSTA1-1. GSBpd is also compared with those of hGSTP1-1[V104,A113].GSBpd, hGSPA1-1.S-benzylglutathione, and mGSTA4-4. 4-S-glutathionyl-5-pentyltetrahydrofuran-2-ol. The comparison provides further evidence that supports the functional roles of R216 and helix alpha9. The lack of mobility of helix alpha9 and/or the lack of electrostatic assistance from R216 may be responsible for the relatively lower activity of hGSTA1-1, mGSTA4-4, and hGSTP1-1 toward (+)-anti-BPDE.
 

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.  
16421451 E.Grahn, M.Novotny, E.Jakobsson, A.Gustafsson, L.Grehn, B.Olin, D.Madsen, M.Wahlberg, B.Mannervik, and G.J.Kleywegt (2006).
New crystal structures of human glutathione transferase A1-1 shed light on glutathione binding and the conformation of the C-terminal helix.
  Acta Crystallogr D Biol Crystallogr, 62, 197-207.
PDB codes: 1pkw 1pkz 1pl1 1pl2 1xwg
17112229 Y.M.Koen, W.Yue, N.A.Galeva, T.D.Williams, and R.P.Hanzlik (2006).
Site-specific arylation of rat glutathione s-transferase A1 and A2 by bromobenzene metabolites in vivo.
  Chem Res Toxicol, 19, 1426-1434.  
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.  
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.

 

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