Evidence for an induced-fit mechanism operating in pi class glutathione transferases.
Three-dimensional structures of the apo form of human pi class glutathione transferase have been determined by X-ray crystallography. The structures suggest the enzyme recognizes its substrate, glutathione, by an induced-fit mechanism. Compared to complexed forms of the enzyme, the environment around the catalytic residue, Tyr 7, remains unchanged in the apoenzyme. This observation supports the view that Tyr 7 does not act as a general base in the reaction mechanism. The observed cooperativity of the dimeric enzyme may be due to the movements of a helix that forms one wall of the active site and, in particular, to movements of a tyrosine residue that is located in the subunit interface.
The Ian Potter Foundation Protein Crystallography Laboratory, St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
A J
AJ
Oakley
M
M
Lo Bello
G
G
Ricci
G
G
Federici
M W
MW
Parker
D001051:Apoenzymes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D019281:Dimerization; D005978:Glutathione / Q000378:metabolism; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D013379:Substrate Specificity; D014443:Tyrosine / Q000737:chemistry
D001051:Apoenzymes; D007527:Isoenzymes; D014443:Tyrosine; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D005978:Glutathione