Key result
Optical melting, NMR, and functional group substitution experiments suggest that GU closing pairs and sheared GA pairs form in the J4/5 loop of the P. carinii group I intron.
The dynamic J4/5 loop presents several possible structures for potential binding of drugs that target group I self-splicing introns.
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May guide intron-targeted drug design; hypothesis-generating for therapeutic application in pathogens.
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 self-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 dynamic 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.
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Schroeder et al. (2003) studied this question. Optical melting, NMR, and functional group substitution experiments suggest that GU closing pairs and sheared GA pairs form in the J4/5 loop of the P. carinii group I intron.
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