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PDBsum entry 1gtu

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protein Protein-protein interface(s) links
Transferase PDB id
1gtu
Jmol
Contents
Protein chain
217 a.a. *
Waters ×63
* Residue conservation analysis
PDB id:
1gtu
Name: Transferase
Title: Ligand-free human glutathione s-transferase m1a-1a
Structure: Glutathione s-transferase. Chain: a, b, c, d. Engineered: yes. Other_details: ligand-free
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: hela. Organ: liver. Cellular_location: cytoplasm. Gene: gstm1a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
Resolution:
2.68Å     R-factor:   0.211     R-free:   0.245
Authors: Y.V.Patskovsky,L.N.Patskovska,I.Listowsky
Key ref:
Y.V.Patskovsky et al. (1999). Functions of His107 in the catalytic mechanism of human glutathione S-transferase hGSTM1a-1a. Biochemistry, 38, 1193-1202. PubMed id: 9930979 DOI: 10.1021/bi982164m
Date:
11-Jun-98     Release date:   02-Feb-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P09488  (GSTM1_HUMAN) -  Glutathione S-transferase Mu 1
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   8 terms 
  Biochemical function     transferase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi982164m Biochemistry 38:1193-1202 (1999)
PubMed id: 9930979  
 
 
Functions of His107 in the catalytic mechanism of human glutathione S-transferase hGSTM1a-1a.
Y.V.Patskovsky, L.N.Patskovska, I.Listowsky.
 
  ABSTRACT  
 
Domain interchange analyses and site-directed mutagenesis indicate that the His107 residue of the human subunit hGSTM1 has a pronounced influence on catalysis of nucleophilic aromatic substitution reactions, and a H107S substitution accounts for the marked differences in the properties of the homologous hGSTM1-1 (His107) and hGSTM4-4 (Ser107) glutathione S-transferases. Reciprocal replacement of His107 and Ser107 in chimeric enzymes results in reciprocal conversion of catalytic properties. With 1-chloro-2, 4-dinitrobenzene as a substrate, the His107 residue primarily influences the pH dependence of catalysis by lowering the apparent pKa of kcat/Km from 7.8 for the Ser107-containing enzymes to 6.3 for the His107-containing enzymes. There is a parallel shift in the pKa for thiolate anion formation of enzyme-bound GSH. Y6F mutations have no effect on the pKa for these enzymes. Crystal structures of hGSTM1a-1a indicate that the imidazole ring of His107 is oriented toward the substrate binding cleft approximately 6 A from the GSH thiol group. Thus, His107 has the potential to act as a general base in proton transfer mediated through an active site water molecule or directly following a modest conformational change, to promote thiolate anion formation. All wild-type enzymes and H107S chimera have nearly identical equilibrium constants for formation of enzyme-GSH complexes (Kd values of 1-2 x 10(-)6 M); however, KmGSH and Ki values for S-methylglutathione inhibition determined by steady-state kinetics are nearly 100-fold higher. The functions of His107 of hGSTM1a-1a are unexpected in view of a substantial body of previous evidence that excluded participation of histidine residues in the catalytic mechanisms of other glutathione S-transferases. Consequences of His107 involvement in catalysis are also substrate-dependent; in contrast to 1-chloro-2,4-dinitrobenzene, for the nucleophilic addition reaction of GSH to ethacrynic acid, the H107S substitution has no effect on catalysis presumably because product release is rate-limiting.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
16385005 N.Hiller, K.Fritz-Wolf, M.Deponte, W.Wende, H.Zimmermann, and K.Becker (2006).
Plasmodium falciparum glutathione S-transferase--structural and mechanistic studies on ligand binding and enzyme inhibition.
  Protein Sci, 15, 281-289.
PDB code: 2aaw
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.  
15489226 M.Katragadda, D.Morikis, and J.D.Lambris (2004).
Thermodynamic studies on the interaction of the third complement component and its inhibitor, compstatin.
  J Biol Chem, 279, 54987-54995.  
14623980 K.Fritz-Wolf, A.Becker, S.Rahlfs, P.Harwaldt, R.H.Schirmer, W.Kabsch, and K.Becker (2003).
X-ray structure of glutathione S-transferase from the malarial parasite Plasmodium falciparum.
  Proc Natl Acad Sci U S A, 100, 13821-13826.
PDB code: 1okt
10737945 J.U.Flanagan, W.King, M.W.Parker, P.G.Board, and G.Chelvanayagam (2000).
Ab initio calculations on hidden modulators of theta class glutathione transferase activity.
  Proteins, 39, 235-243.  
10652317 Y.V.Patskovsky, L.N.Patskovska, and I.Listowsky (2000).
The enhanced affinity for thiolate anion and activation of enzyme-bound glutathione is governed by an arginine residue of human Mu class glutathione S-transferases.
  J Biol Chem, 275, 3296-3304.
PDB code: 2gtu
  10631991 L.O.Hansson, R.Bolton-Grob, M.Widersten, and B.Mannervik (1999).
Structural determinants in domain II of human glutathione transferase M2-2 govern the characteristic activities with aminochrome, 2-cyano-1,3-dimethyl-1-nitrosoguanidine, and 1,2-dichloro-4-nitrobenzene.
  Protein Sci, 8, 2742-2750.  
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.