共查询到20条相似文献,搜索用时 15 毫秒
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《Molecular cell》2021,81(16):3386-3399.e10
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Arnold JJ Vignuzzi M Stone JK Andino R Cameron CE 《The Journal of biological chemistry》2005,280(27):25706-25716
The kinetic, thermodynamic, and structural basis for fidelity of nucleic acid polymerases remains controversial. An understanding of viral RNA-dependent RNA polymerase (RdRp) fidelity has become a topic of considerable interest as a result of recent experiments that show that a 2-fold increase in fidelity attenuates viral pathogenesis and a 2-fold decrease in fidelity reduces viral fitness. Here we show that a conformational change step preceding phosphoryl transfer is a key fidelity checkpoint for the poliovirus RdRp (3Dpol). We provide evidence that this conformational change step is orientation of the triphosphate into a conformation suitable for catalysis, suggesting a kinetic and structural model for RdRp fidelity that can be extrapolated to other classes of nucleic acid polymerases. Finally, we show that a site remote from the catalytic center can control this checkpoint, which occurs at the active site. Importantly, similar connections between a remote site and the active site exist in a wide variety of viral RdRps. The capacity for sites remote from the catalytic center to alter fidelity suggests new possibilities for targeting the viral RdRp for antiviral drug development. 相似文献
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Hemming SA Jansma DB Macgregor PF Goryachev A Friesen JD Edwards AM 《The Journal of biological chemistry》2000,275(45):35506-35511
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Electron crystal structure of an RNA polymerase II transcription elongation complex. 总被引:2,自引:0,他引:2
C L Poglitsch G D Meredith A L Gnatt G J Jensen W H Chang J Fu R D Kornberg 《Cell》1999,98(6):791-798
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