Three-dimensional structure of class pi glutathione S-transferase from human placenta in complex with S-hexylglutathione at 2.8 A resolution.
The three-dimensional structure of human class pi glutathione S-transferase from placenta (hGSTP1-1), a homodimeric enzyme, has been solved by Patterson search methods and refined at 2.8 A resolution to a final crystallographic R-factor of 19.6% (8.0 to 2.8 A resolution). Subunit folding topology, subunit overall structure and subunit association closely resembles the structure of porcine class pi glutathione S-transferase. The binding site of a competitive inhibitor, S-hexylglutathione, is analyzed and the locations of the binding regions for glutathione (G-site) and electrophilic substrates (H-site) are determined. The specific interactions between protein and the inhibitor's glutathione peptide are the same as those observed between glutathione sulfonate and the porcine isozyme. The H-site is located adjacent to the G-site, with the hexyl moiety lying above a segment (residues 8 to 10) connecting strand beta 1 and helix alpha A where it is in hydrophobic contact with Tyr7, Phe8, Val10, Val35 and Tyr106. Catalytic models are discussed on the basis of the molecular structure.
Reinemer
P
P
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Dirr
H W
HW
Ladenstein
R
R
Huber
R
R
Lo Bello
M
M
Federici
G
G
Parker
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003461:Crystallography; D005583:Fourier Analysis; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000648:ultrastructure*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010315:Particle Accelerators; D010920:Placenta / Q000201:enzymology; D011485:Protein Binding; D011487:Protein Conformation; D013552:Swine
D046911:Macromolecular Substances; D005982:Glutathione Transferase; D005978:Glutathione; C033550:hexylglutathione