Gogos Arhonda, Shapiro Lawrence
Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Structure. 2002 Dec;10(12):1669-76. doi: 10.1016/s0969-2126(02)00906-1.
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.
谷胱甘肽合酶催化谷胱甘肽生物合成中最后一步依赖ATP的反应，即由γ-谷氨酰半胱氨酸和甘氨酸形成谷胱甘肽。我们已经确定了酵母谷胱甘肽合酶的两种结构形式：未结合状态（分辨率为2.3 Å）以及与底物γ-谷氨酰半胱氨酸、ATP类似物AMP-PNP和两个镁离子结合的状态（分辨率为1.8 Å）。这些结构表明，在底物结合时，结构域的大幅运动使酶从开放的未结合配体形式转变为封闭构象，其中蛋白质结构域在活性位点完全包围底物。
