Glutathione induces helical formation in the carboxy terminus of human glutathione transferase A1-1.
Glutathione induces helical formation in the carboxy terminus of human glutathione transferase A1-1.
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谷胱甘肽诱导人谷胱甘肽转移酶 A1-1 羧基末端形成螺旋。
DOI：
10.1021/bi0363329
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Rule,GordonS
中科院分区：
文献类型：
--
作者：
Zhan,Yiping;Rule,GordonS
用高分辨核磁共振方法研究了人α谷胱甘肽转移酶A1-1的C-末端区域的结构和动力学性质。晶体学和荧光测量的基础上，这13个残基的酶段被假定为无序的unliganded酶。当产物或产物类似物结合时，在晶体结构中观察到C-末端α-螺旋。当底物之一谷胱甘肽（GSH）结合时，存在关于该区域结构的数据。这里提出的NMR研究表明，在unliganded蛋白质，该区域的蛋白质样品不同的构象，最有可能是一个合奏的螺旋状结构。添加GSH或GSH与依他尼酸（EASG）的结合物可使该片段成为稳定的α-螺旋。在GSH复合物中，该螺旋的末端在毫秒和纳秒时间尺度上都表现出动态行为。相比之下，没有证据表明毫秒动力学在EASG复杂。配体诱导的酶的有序化降低了酶对其产物的固有亲和力，促进了酶的周转。
The structure and dynamic properties of the C-terminal region of the human class alpha glutathione transferase A1-1 have been investigated with high-resolution NMR methods. On the basis of crystallographic and fluorescence measurements, this 13-residue segment of the enzyme is presumed to be disordered in the unliganded enzyme. When the product or product analogue is bound, a C-terminal α-helix is observed in crystal structures. Conflicting data exists regarding the structure of this region when one of the substrates, glutathione (GSH), is bound. The NMR studies presented here show that in the unliganded protein, this region of the protein samples different conformations, most likely an ensemble of helix-like structures. Addition of either GSH or the conjugate between GSH and ethacrynic acid (EASG) causes this segment to become a stable α-helix. In the GSH complex, the ends of this helix exhibit dynamic behavior on both the millisecond and nanosecond time scales. In contrast, there is no evidence of millisecond dynamics in the EASG complex. The ligand-induced ordering of the enzyme reduces the intrinsic affinity of the enzyme for its product, facilitating enzymatic turnover.