Large conformational changes in the catalytic cycle of glutathione synthase.

Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.

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.

PMID: 12467574 [PubMed - indexed for MEDLINE]