Structural basis for double-sieve discrimination of L-valine from L-isoleucine and L-threonine by the complex of tRNAVal and valyl-tRNA synthetase
Structural basis for double-sieve discrimination of L-valine from L-isoleucine and L-threonine by the complex of tRNAVal and valyl-tRNA synthetase
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DOI：
10.1016/s0092-8674(00)00182-3
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发表时间：
2000-11-22
期刊：
影响因子：
64.5
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
--
作者：
Fukai, S;Nureki, O;Yokoyama, S
Valyl-tRNA合成酶（ValRS）通过tRNA依赖的“双筛”机制严格区分同源L-缬氨酸与较大的L-异亮氨酸和等排L-苏氨酸。在这项研究中，我们确定了2.9埃的晶体结构的复合物嗜热栖热菌ValRS，tRNA（瓦尔），和类似物的Val-腺苷酸中间体。类似物结合在口袋中，其中Pro（41）允许容纳氨基酰化结构域上的瓦尔和Thr部分，但排除lie部分（第一筛）。水解不正确合成的Thr-tRNA（瓦尔）的编辑结构域结合到tRNA（瓦尔）的3'腺苷。发现连续的口袋容纳Thr部分，但不容纳瓦尔部分（第二筛）。此外，另一个Thr结合口袋的Thr-腺苷酸水解的编辑域建议。
Valyl-tRNA synthetase (ValRS) strictly discriminates the cognate L-valine from the larger L-isoleucine and the isosteric L-threonine by the tRNA-dependent "double sieve" mechanism. In this study, we determined the 2.9 Angstrom crystal structure of a complex of Thermus thermophilus ValRS, tRNA(Val), and an analog of the Val-adenylate intermediate. The analog is bound in a pocket, where Pro(41) allows accommodation of the Val and Thr moieties but precludes the lie moiety (the first sieve), on the aminoacylation domain, The editing domain, which hydrolyzes incorrectly synthesized Thr-tRNA(Val), is bound to the 3' adenosine of tRNA(Val). A contiguous pocket was found to accommodate the Thr moiety, but not the Val moiety (the second sieve). Furthermore, another Thr binding pocket for Thr-adenylate hydrolysis was suggested on the editing domain.