Large conformational changes in the catalytic cycle of glutathione synthase.
Glutathione synthase catalyzes the final ATP-dependent step in glutathione biosynthesis, the formation of glutathione from gamma-glutamylcysteine and glycine. We have determined structures of yeast glutathione synthase in two forms: unbound (2.3 A resolution) and bound to its substrate gamma-glutamylcysteine, the ATP analog AMP-PNP, and two magnesium ions (1.8 A resolution). These structures reveal that upon substrate binding, large domain motions convert the enzyme from an open unliganded form to a closed conformation in which protein domains completely surround the substrate in the active site.
Gogos
Arhonda
A
Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Shapiro
Lawrence
L
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D002384:Catalysis; D005981:Glutathione Synthase / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D008024:Ligands; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D005981:Glutathione Synthase; D008274:Magnesium