Insights into editing from an Ile-tRNA synthetase structure with tRNAIle and mupirocin

Insights into editing from an Ile-tRNA synthetase structure with tRNAIle and mupirocin
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DOI:
10.1126/science.285.5430.1074
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发表时间:
1999-08-13
期刊:
影响因子:
56.9
通讯作者:
Steitz, TA
Steitz, TA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Silvian, LF;Wang, JM;Steitz, TA

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异亮氨酰转移RNA(tRNA)合成酶(IleRS)在其合成活性位点将Ire连接到tRNA(Ile),并在其编辑活性位点水解不正确酰化的氨基酸。金黄色葡萄球菌IleRS与tRNA(Ile)和莫匹罗星复合的2.2埃分辨率晶体结构显示tRNA(Ile)的受体链呈连续堆叠的A型构象,3'末端核苷酸位于编辑活性位点。为了将3'末端定位在合成活性位点中,受体链必须采用与其合成酶复合的tRNA(Gln)中所见的发夹构象。IleRS的氨基酸编辑活性可能是由于在合成和编辑活性位点之间穿梭的不正确产物,这使人想起DNA聚合酶的编辑机制。
Isoleucyl-transfer RNA (tRNA) synthetase (IleRS) joins Ire to tRNA(Ile) at its synthetic active site and hydrolyzes incorrectly acylated amino acids at its editing active site. The 2.2 angstrom resolution crystal structure of Staphylococcus aureus IleRS complexed with tRNA(Ile) and Mupirocin shows the acceptor strand of the tRNA(Ile) in the continuously stacked, A-form conformation with the 3' terminal nucleotide in the editing active site. To position the 3' terminus in the synthetic active site, the acceptor strand must adopt the hairpinned conformation seen in tRNA(Gln) complexed with its synthetase, The amino acid editing activity of the IleRS may result from the incorrect products shuttling between the synthetic and editing active sites, which is reminiscent of the editing mechanism of DNA polymerases.