9MQS

CryoEM Structure of the Candida albicans Group I Intron-GMP Complex

Summary for 9MQS

• Entry DOI: 10.2210/pdb9mqs/pdb
• EMDB information: 48538
• Descriptor: RNA (332-MER), CALCIUM ION, POTASSIUM ION, ... (5 entities in total)
• Functional Keywords: intron, group i, splicing, rna
• Biological source: Candida albicans
• Total number of polymer chains: 1
• Total formula weight: 107409.93

Authors

Chung, K.,Xu, L.,Liu, T.,Pyle, A. (deposition date: 2025-01-06, release date: 2025-04-30, Last modification date: 2025-05-28)

Primary citation

Liu, T.,Xu, L.,Chung, K.,Sisto, L.J.,Hwang, J.,Zhang, C.,Van Zandt, M.C.,Pyle, A.M.
Molecular insights into de novo small-molecule recognition by an intron RNA structure.
Proc.Natl.Acad.Sci.USA, 122:e2502425122-e2502425122, 2025

PubMed Abstract: Despite the promise of vastly expanding the druggable genome, rational design of RNA-targeting ligands remains challenging as it requires the rapid identification of hits and visualization of the resulting cocomplexes for guiding optimization. Here, we leveraged high-throughput screening, medicinal chemistry, and structural biology to identify a de novo splicing inhibitor against a large and highly folded fungal group I intron. High-resolution cryoEM structures of the intron in different liganded states not only reveal molecular interactions that rationalize experimental structure-activity relationship but also shed light on a unique strategy whereby RNA-associated metal ions and RNA conformation exhibit exceptional plasticity in response to small-molecule binding. This study reveals general principles that govern RNA-ligand recognition, the interplay between chemical bonding specificity, and dynamic responses within an RNA target.

PubMed: 40339124
DOI: 10.1073/pnas.2502425122

Experimental method

ELECTRON MICROSCOPY (3.1 Å)