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Thermodynamic stability and structural features of the J4/5 loop in a pneumocystis carinii group I intron

机译：卡氏肺孢子虫第I组内含子的J4 / 5环的热力学稳定性和结构特征

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摘要

The J4/5 loop of the group I intron in the mouse-derived fungal pathogen Pneumocystis carinii is the docking site for the first step of the RNA-catalyzed elf-splicing reaction and thus is a model of a potential drug target.This purine-rich asymmetric internal loop,5'GGAAG/3'UAGU,is also thermodynamically more stable than other internal loops with two GU closing pairs and three nucleotides opposite two nucleotides.The results from optical melting,nuclear magnetic resonance spectroscopy,and functional group substitution experiments suggest that the GU closing pairs form and that sheared GA pairs form in the internal loop.The NMR spectra show evidence of conformational dynamics,and several GA pairings are possible.Thus,this dynaic loop presents several possible structures for potential binding of drugs that target group I self-splicing introns.The results also contribute to understanding the structural and dynamic basis for the function and thermodynamic stability of this loop.
机译：小鼠衍生的真菌病原体卡氏肺孢子虫（Pneumocystis carinii）中第I组内含子的J4 / 5环是RNA催化的自我剪接反应第一步的对接位点，因此是潜在药物靶点的模型。丰富的不对称内部环（5'GGAAG / 3'UAGU）在热力学上也比其他内部环（具有两个GU封闭对和三个与两个核苷酸相对的核苷酸）更稳定。来自光学熔解，核磁共振光谱和官能团取代实验的结果NMR谱显示构象动力学证据，并且可能存在多个GA配对。因此，该动力学环为靶向药物的潜在结合提供了几种可能的结构。该结果还有助于理解该环的功能和热力学稳定性的结构和动力学基础。

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