PDBsum entry 1gtu

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protein Protein-protein interface(s) links
Transferase PDB id
Protein chain
217 a.a. *
Waters ×63
* Residue conservation analysis
PDB id:
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)
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
11-Jun-98     Release date:   02-Feb-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P09488  (GSTM1_HUMAN) -  Glutathione S-transferase Mu 1
218 a.a.
217 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
+ 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  


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.
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.  
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