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PDBsum entry 4gtu

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protein Protein-protein interface(s) links
Transferase PDB id
4gtu
Jmol
Contents
Protein chain
(+ 2 more) 217 a.a. *
* Residue conservation analysis
PDB id:
4gtu
Name: Transferase
Title: Ligand-free homodimeric human glutathione s-transferase m4-4
Structure: Glutathione s-transferase. Chain: a, b, c, d, e, f, g, h. Engineered: yes. Other_details: ligand-free, homodimer
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: hepg2. Cellular_location: cytoplasm. Gene: gstm4. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Other_details: the gstm4 cdna was amplified using rt-pcr an
Biol. unit: Dimer (from PQS)
Resolution:
3.30Å     R-factor:   0.245     R-free:   0.315
Authors: Y.V.Patskovsky,L.N.Patskovska,I.Listowsky
Key ref:
Y.V.Patskovsky et al. (1999). An asparagine-phenylalanine substitution accounts for catalytic differences between hGSTM3-3 and other human class mu glutathione S-transferases. Biochemistry, 38, 16187-16194. PubMed id: 10587441 DOI: 10.1021/bi991714t
Date:
12-May-99     Release date:   14-Jan-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q03013  (GSTM4_HUMAN) -  Glutathione S-transferase Mu 4
Seq:
Struc:
218 a.a.
217 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     cytoplasm   2 terms 
  Biological process     metabolic process   6 terms 
  Biochemical function     transferase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi991714t Biochemistry 38:16187-16194 (1999)
PubMed id: 10587441  
 
 
An asparagine-phenylalanine substitution accounts for catalytic differences between hGSTM3-3 and other human class mu glutathione S-transferases.
Y.V.Patskovsky, L.N.Patskovska, I.Listowsky.
 
  ABSTRACT  
 
The hGSTM3 subunit, which is preferentially expressed in germ-line cells, has the greatest sequence divergence among the human mu class glutathione S-transferases. To determine a structural basis for the catalytic differences between hGSTM3-3 and other mu class enzymes, chimeric proteins were designed by modular interchange of the divergent C-terminal domains of hGSTM3 and hGSTM5 subunits. Replacement of 24 residues of the C-terminal segment of either subunit produced chimeric enzymes with catalytic properties that reflected those of the wild-type enzyme from which the C-terminus had been derived. Deletion of the tripeptide C-terminal extension found only in the hGSTM3 subunit had no effect on catalysis. The crystal structure determined for a ligand-free hGSTM3 subunit indicates that an Asn212 residue of the C-terminal domain is near a hydrophobic cluster of side chains formed in part by Ile13, Leu16, Leu114, Ile115, Tyr119, Ile211, and Trp218. Accordingly, a series of point mutations were introduced into the hGSTM3 subunit, and it was indeed determined that a Y119F mutation considerably enhanced the turnover rate of the enzyme for nucleophilic aromatic substitution reactions. A more striking effect was observed for a double mutant (Y119F/N212F) which had a k(cat)/K(m)(CDNB) value of 7.6 x 10(5) s(-)(1) M(-)(1) as compared to 4.9 x 10(3) s(-)(1) M(-)(1) for the wild-type hGSTM3-3 enzyme. The presence of a polar Asn212 in place of a Phe residue found in the cognate position of other mu class glutathione S-transferases, therefore, has a marked influence on catalysis by hGSTM3-3.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18932202 H.Dehari, T.Tchaikovskaya, E.Rubashevsky, R.Sellers, and I.Listowsky (2009).
The proximal promoter governs germ cell-specific expression of the mouse glutathione transferase mGstm5 gene.
  Mol Reprod Dev, 76, 379-388.  
15686533 I.Listowsky (2005).
Proposed intracellular regulatory functions of glutathione transferases by recognition and binding to S-glutathiolated proteins.
  J Pept Res, 65, 42-46.  
15822171 J.D.Hayes, J.U.Flanagan, and I.R.Jowsey (2005).
Glutathione transferases.
  Annu Rev Pharmacol Toxicol, 45, 51-88.  
15247628 N.Tetlow, A.Robinson, T.Mantle, and P.Board (2004).
Polymorphism of human mu class glutathione transferases.
  Pharmacogenetics, 14, 359-368.  
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