The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus and its complexes with ATP and asparaginyl-adenylate:: the mechanism of discrimination between asparagine and aspartic acid
The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus and its complexes with ATP and asparaginyl-adenylate:: the mechanism of discrimination between asparagine and aspartic acid
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DOI：
10.1093/emboj/17.10.2947
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发表时间：
1998-05-15
期刊：
影响因子：
11.4
通讯作者：
Leberman, R
中科院分区：
文献类型：
--
作者：
Berthet-Colominas, C;Seignovert, L;Leberman, R
嗜热菌天冬酰胺酰-tRNA合成酶的晶体结构已通过多重同晶置换得到解析，并以2.6埃分辨率进行精修。这是待确定的三个 IIb 类氨酰基-tRNA 合成酶结构中的最后一个。正如一级序列比较所预期的那样，天冬酰胺酰-tRNA合成酶和天冬氨酰-tRNA合成酶的三级结构之间存在显着的相似性，并且除了三个关键差异外，大多数活性位点残基是相同的。天冬酰胺酰-tRNA 合成酶与不可水解的天冬酰胺酰腺苷酸类似物复合的 2.65 埃结构可以详细解释这三种差异如何使每种酶区分它们各自和非常相似的氨基酸底物天冬酰胺和天冬氨酸。此外，天冬酰胺酰-tRNA合成酶与ATP的复合物的结构显示出与之前在丝氨酰-tRNA合成酶-ATP复合物中观察到的完全相同的三个二价阳离子的构型，表明这是II类合成酶的一般特征。天冬酰胺酰和天冬氨酰-tRNA 合成酶以及这两种酶与氨依赖性天冬酰胺合成酶的结构相似性表明，这三种酶是从共同祖先进化而来的。
The crystal structure of Thermos thermophilus asparaginyl-tRNA synthetase has been solved by multiple isomorphous replacement and refined at 2.6 Angstrom resolution. This is the last of the three class IIb aminoacyl-tRNA synthetase structures to be determined. As expected from primary sequence comparisons, there are remarkable similarities between the tertiary structures of asparaginyl-tRNA synthetase and aspartyl-tRNA synthetase, and most of the active site residues are identical except for three key differences. The structure at 2.65 Angstrom of asparaginyl-tRNA synthetase complexed with a non-hydrolysable analogue of asparaginyl-adenylate permits a detailed explanation of how these three differences allow each enzyme to discriminate between their respective and very similar amino acid substrates, asparagine and aspartic acid. In addition, a structure of the complex of asparaginyl-tRNA synthetase with ATP shows exactly the same configuration of three divalent cations as previously observed in the seryl-tRNA synthetase-ATP complex, showing that this a general feature of class II synthetases. The structural similarity of asparaginyl-and aspartyl-tRNA synthetases as well as that of both enzymes to the ammonia-dependent asparagine synthetase suggests that these three enzymes have evolved relatively recently from a common ancestor.