Shifting substrate specificity of human glutathione transferase (from class Pi to class alpha) by a single point mutation.
Substrate selectivity, among glutathione transferase (GST) isoenzymes, appears to be determined by a few residues. As part of study to determine which residues are class-specific determinants, Tyr 108 (an important residue of the class Pi) has been changed to a valine, the structural equivalent of a class Alpha enzyme. Using a panel of selected substrates, "diagnostic" for either class Pi or Alpha, it is shown here that this single mutation significantly alters the catalytic properties of the class Pi enzyme and shifts the substrate specificity of the enzyme toward that of the class Alpha enzyme.
Nuccetelli
M
M
Department of Biology, University of Rome "Tor Vergata," Via della Ricerca Scientifica, Rome, 00133, Italy.
Mazzetti
A P
AP
Rossjohn
J
J
Parker
M W
MW
Board
P
P
Caccuri
A M
AM
Federici
G
G
Ricci
G
G
Lo Bello
M
M
D000595:Amino Acid Sequence; D020134:Catalytic Domain; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014443:Tyrosine
D007527:Isoenzymes; D011994:Recombinant Proteins; D014443:Tyrosine; D005982:Glutathione Transferase