Uneven spread of cis- and trans-editing aminoacyl-tRNA synthetase domains within translational compartments of P. falciparum.
Uneven spread of cis- and trans-editing aminoacyl-tRNA synthetase domains within translational compartments of P. falciparum.
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DOI：
10.1038/srep00188
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发表时间：
2011
影响因子：
4.6
通讯作者：
Sharma, Amit
中科院分区：
文献类型：
--
作者：
Khan, Sameena;Sharma, Arvind;Jamwal, Abhishek;Sharma, Vinay;Pole, Anil Kumar;Thakur, Kamal Kishor;Sharma, Amit
氨酰化的准确性取决于在氨基酸与同源tRNA连接期间保持保真度。顺式和反式编辑蛋白质因子在蛋白质翻译过程中进行质量控制，36个恶性疟原虫氨酰-tRNA合成酶（阿尔斯）组件中有8个包含典型的推定编辑模块。基于这8个aaRSs的表达和定位概况，我们提出了一个不对称分布之间的寄生虫细胞质和其顶质体的推定的编辑域含有aaRSs。我们还表明，单拷贝丙氨酰和苏氨酰-tRNA合成酶的双重目标寄生虫的细胞质和顶质体。两种独特的合成酶的这种双极性存在为靶向其在双寄生虫隔室中的氨酰化和编辑活性的抑制剂提供了机会。我们使用这种方法来确定对丙氨酰和苏氨酰-tRNA合成酶的特异性抑制剂。这种抑制剂的进一步发展可能会导致抗寄生虫药，同时阻止蛋白质翻译在两个关键的寄生虫细胞器，一个更广泛的适用性的病原体控制的策略。
Accuracy of aminoacylation is dependent on maintaining fidelity during attachment of amino acids to cognate tRNAs. Cis- and trans-editing protein factors impose quality control during protein translation, and 8 of 36 Plasmodium falciparum aminoacyl-tRNA synthetase (aaRS) assemblies contain canonical putative editing modules. Based on expression and localization profiles of these 8 aaRSs, we propose an asymmetric distribution between the parasite cytoplasm and its apicoplast of putative editing-domain containing aaRSs. We also show that the single copy alanyl- and threonyl-tRNA synthetases are dually targeted to parasite cytoplasm and apicoplast. This bipolar presence of two unique synthetases presents opportunity for inhibitor targeting their aminoacylation and editing activities in twin parasite compartments. We used this approach to identify specific inhibitors against the alanyl- and threonyl-tRNA synthetases. Further development of such inhibitors may lead to anti-parasitics which simultaneously block protein translation in two key parasite organelles, a strategy of wider applicability for pathogen control.
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影响因子：
4.4
作者：
Bhatt TK;Kapil C;Khan S;Jairajpuri MA;Sharma V;Santoni D;Silvestrini F;Pizzi E;Sharma A
通讯作者：
Sharma A
DOI：
10.1073/pnas.1011560108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Istvan, Eva S.;Dharia, Neekesh V.;Goldberg, Daniel E.
通讯作者：
Goldberg, Daniel E.
影响因子：
14.9
作者：
Letunic I;Doerks T;Bork P
通讯作者：
Bork P
影响因子：
14.9
作者：
Bahl, A;Brunk, B;Whetzel, P
通讯作者：
Whetzel, P
DOI：
10.1074/jbc.m109.038562
发表时间：
2010-02-19
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bhatt TK;Yogavel M;Wydau S;Berwal R;Sharma A
通讯作者：
Sharma A