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PDBsum entry 1xwk

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1xwk
Jmol
Contents
Protein chain
217 a.a. *
Ligands
GDN ×3
Waters ×159
* Residue conservation analysis
PDB id:
1xwk
Name: Transferase
Title: 2.3 angstrom resolution crystal structure of human glutathione s-transferase m1a-1a complexed with glutathionyl-s-dinitrobenzene
Structure: Glutathione s-transferase mu 1. Chain: a, b, c. Synonym: gstm1-1, gst class-mu 1, gstm1a-1a, gstm1b-1b, hb subunit 4, gth4. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gstm1, gst1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
Resolution:
2.30Å     R-factor:   0.243     R-free:   0.281
Authors: Y.Patskovsky,L.Patskovska,S.C.Almo,I.Listowsky
Key ref:
Y.Patskovsky et al. (2006). Transition state model and mechanism of nucleophilic aromatic substitution reactions catalyzed by human glutathione S-transferase M1a-1a. Biochemistry, 45, 3852-3862. PubMed id: 16548513 DOI: 10.1021/bi051823+
Date:
01-Nov-04     Release date:   21-Dec-04    
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
Bound ligand (Het Group name = GDN)
matches with 62.00% similarity
= 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/bi051823+ Biochemistry 45:3852-3862 (2006)
PubMed id: 16548513  
 
 
Transition state model and mechanism of nucleophilic aromatic substitution reactions catalyzed by human glutathione S-transferase M1a-1a.
Y.Patskovsky, L.Patskovska, S.C.Almo, I.Listowsky.
 
  ABSTRACT  
 
An active site His107 residue distinguishes human glutathione S-transferase hGSTM1-1 from other mammalian Mu-class GSTs. The crystal structure of hGSTM1a-1a with bound glutathione (GSH) was solved to 1.9 A resolution, and site-directed mutagenesis supports the conclusion that a proton transfer occurs in which bound water at the catalytic site acts as a primary proton acceptor from the GSH thiol group to transfer the proton to His107. The structure of the second substrate-binding site (H-site) was determined from hGSTM1a-1a complexed with 1-glutathionyl-2,4-dinitrobenzene (GS-DNB) formed by a reaction in the crystal between GSH and 1-chloro-2,4-dinitrobenzene (CDNB). In that structure, the GSH-binding site (G-site) is occupied by the GSH moiety of the product in the same configuration as that of the enzyme-GSH complex, and the dinitrobenzene ring is anchored between the side chains of Tyr6, Leu12, His107, Met108, and Tyr115. This orientation suggested a distinct transition state that was substantiated from the structure of hGSTM1a-1a complexed with transition state analogue 1-S-(glutathionyl)-2,4,6-trinitrocyclohexadienate (Meisenheimer complex). Kinetic data for GSTM1a-1a indicate that kcat(CDNB) for the reaction is more than 3 times greater than kcat(FDNB), even though the nonenzymatic second-order rate constant is more than 50-fold greater for 1-fluoro-2,4-dinitrobenzene (FDNB), and the product is the same for both substrates. In addition, Km(FDNB) is about 20 times less than Km(CDNB). The results are consistent with a mechanism in which the formation of the transition state is rate-limiting in the nucleophilic aromatic substitution reactions. Data obtained with active-site mutants support transition states in which Tyr115, Tyr6, and His107 side chains are involved in the stabilization of the Meisenheimer complex via interactions with the ortho nitro group of CDNB or FDNB and provide insight into the means by which GSTs adapt to accommodate different substrates.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20143451 A.J.Salazar-Medina, L.García-Rico, K.D.García-Orozco, E.Valenzuela-Soto, C.A.Contreras-Vergara, R.Arreola, A.Arvizu-Flores, and R.R.Sotelo-Mundo (2010).
Inhibition by Cu2+ and Cd2+ of a mu-class glutathione S-transferase from shrimp Litopenaeus vannamei.
  J Biochem Mol Toxicol, 24, 218-222.  
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