spacer
spacer

PDBsum entry 2vct

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Transferase PDB id
2vct
Jmol
Contents
Protein chain
(+ 2 more) 221 a.a. *
Ligands
ASD ×4
Waters ×1625
* Residue conservation analysis
PDB id:
2vct
Name: Transferase
Title: Glutathione transferase a2-2 in complex with delta-4- andostrene-3-17-dione
Structure: Glutathione s-transferase a2. Chain: a, b, c, d, e, f, g, h. Synonym: glutathione-s-transferase a2-2, gth2, ha subunit 2, gst-gamma, gsta2-2, gst class-alpha member 2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.10Å     R-factor:   0.221     R-free:   0.288
Authors: K.Tars,B.Olin,B.Mannervik
Key ref: K.Tars et al. (2010). Structural basis for featuring of steroid isomerase activity in alpha class glutathione transferases. J Mol Biol, 397, 332-340. PubMed id: 20083122 DOI: 10.1016/j.jmb.2010.01.023
Date:
27-Sep-07     Release date:   28-Oct-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P09210  (GSTA2_HUMAN) -  Glutathione S-transferase A2
Seq:
Struc:
222 a.a.
221 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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   3 terms 
  Biological process     metabolic process   6 terms 
  Biochemical function     transferase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2010.01.023 J Mol Biol 397:332-340 (2010)
PubMed id: 20083122  
 
 
Structural basis for featuring of steroid isomerase activity in alpha class glutathione transferases.
K.Tars, B.Olin, B.Mannervik.
 
  ABSTRACT  
 
Glutathione transferases (GSTs) are abundant enzymes catalyzing the conjugation of hydrophobic toxic substrates with glutathione. In addition to detoxication, human GST A3-3 displays prominent steroid double-bond isomerase activity; e.g. transforming Delta(5)-androstene-3-17-dione into Delta(4)-androstene-3-17-dione (AD). This chemical transformation is a crucial step in the biosynthesis of steroids, such as testosterone and progesterone. In contrast to GST A3-3, the homologous GST A2-2 does not show significant steroid isomerase activity. We have solved the 3D structures of human GSTs A2-2 and A3-3 in complex with AD. In the GST A3-3 crystal structure, AD was bound in an orientation suitable for the glutathione (GSH)-mediated catalysis to occur. In GST A2-2, however, AD was bound in a completely different orientation with its reactive double bond distant from the GSH-binding site. The structures illustrate how a few amino acid substitutions in the active site spectacularly alter the binding mode of the steroid substrate in relation to the conserved catalytic groups and an essentially fixed polypeptide chain conformation. Furthermore, AD did not bind to the GST A2-2-GSH complex. Altogether, these results provide a first-time structural insight into the steroid isomerase activity of any GST and explain the 5000-fold difference in catalytic efficiency between GSTs A2-2 and A3-3. More generally, the structures illustrate how dramatic diversification of functional properties can arise via minimal structural alterations. We suggest a novel structure-based mechanism of the steroid isomerization reaction.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20673231 N.Fedulova, F.Raffalli-Mathieu, and B.Mannervik (2010).
Porcine glutathione transferase Alpha 2-2 is a human GST A3-3 analogue that catalyses steroid double-bond isomerization.
  Biochem J, 431, 159-167.  
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.