Functional context, biosynthesis, and genetic encoding of pyrrolysine.

Functional context, biosynthesis, and genetic encoding of pyrrolysine.
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DOI:
10.1016/j.mib.2011.04.001
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发表时间:
2011-06
影响因子:
5.4
通讯作者:
Krzycki, Joseph A.
Krzycki, Joseph A.
中科院分区:
生物学2区
文献类型:
--
作者:
Gaston, Marsha A.;Jiang, Ruisheng;Krzycki, Joseph A.

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在甲烷八叠球菌属中,甲胺甲基转移酶基因中的琥珀密码子被翻译为第22个氨基酸吡咯赖氨酸。已在四个古细菌属和五个细菌属(包括一个人类病原体)中鉴定了负责的pyl基因和含琥珀密码子的甲基转移酶基因。在大肠pylBCD基因产物可由两个赖氨酸合成吡咯赖氨酸,pylTS基因产物可直接将吡咯赖氨酸掺入蛋白质中。在提出的生物合成途径中,PylB从赖氨酸形成甲基鸟氨酸,其通过PylC与另一个赖氨酸连接,并通过PylD氧化为吡咯赖氨酸。吡咯赖氨酰-tRNA合成酶(古细菌PylS或细菌PylSc)的催化结构域的结构揭示了tRNAPyl和吡咯赖氨酸的结合位点。PylS和tRNAPyl现在被用作重组系统中的正交对,用于将有用的修饰的氨基酸引入蛋白质中。
In Methanosarcina spp., amber codons in methylamine methyltransferase genes are translated as the 22nd amino acid, pyrrolysine. The responsible pyl genes plus amber-codon containing methyltransferase genes have been identified in four archaeal and five bacterial genera, including one human pathogen. In E. coli, the recombinant pylBCD gene products biosynthesize pyrrolysine from two lysine and the pylTS gene products direct pyrrolysine incorporation into protein. In the proposed biosynthetic pathway, PylB forms methylornithine from lysine, which is joined to another lysine by PylC, and oxidized to pyrrolysine by PylD. Structures of the catalytic domain of pyrrolysyl-tRNA synthetase (archaeal PylS or bacterial PylSc) revealed binding sites for tRNAPyl and pyrrolysine. PylS and tRNAPyl are now being exploited as an orthogonal pair in recombinant systems for introduction of useful modified amino acids into proteins.
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