8RUN

Structure of Oceanobacillus iheyensis group II intron in the presence of Li+, Mg2+, and ARN25850

8RUN の概要

• エントリーDOI: 10.2210/pdb8run/pdb
• 分子名称: Domains 1-5, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, 2-[2,6-bis(bromanyl)-3,4,5-tris(oxidanyl)phenyl]carbonyl-~{N}-(2-pyrrolidin-1-ylethyl)-1-benzofuran-5-carboxamide, ... (5 entities in total)
• 機能のキーワード: ribozyme, metalloenzyme, self-splicing, retrotransposition, rna
• 由来する生物種: Oceanobacillus iheyensis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 129717.15

構造登録者

Silvestri, I.,Marcia, M. (登録日: 2024-01-31, 公開日: 2024-06-19, 最終更新日: 2024-07-03)

主引用文献

Silvestri, I.,Manigrasso, J.,Andreani, A.,Brindani, N.,Mas, C.,Reiser, J.B.,Vidossich, P.,Martino, G.,McCarthy, A.A.,De Vivo, M.,Marcia, M.
Targeting the conserved active site of splicing machines with specific and selective small molecule modulators.
Nat Commun, 15:4980-4980, 2024

PubMed Abstract: The self-splicing group II introns are bacterial and organellar ancestors of the nuclear spliceosome and retro-transposable elements of pharmacological and biotechnological importance. Integrating enzymatic, crystallographic, and simulation studies, we demonstrate how these introns recognize small molecules through their conserved active site. These RNA-binding small molecules selectively inhibit the two steps of splicing by adopting distinctive poses at different stages of catalysis, and by preventing crucial active site conformational changes that are essential for splicing progression. Our data exemplify the enormous power of RNA binders to mechanistically probe vital cellular pathways. Most importantly, by proving that the evolutionarily-conserved RNA core of splicing machines can recognize small molecules specifically, our work provides a solid basis for the rational design of splicing modulators not only against bacterial and organellar introns, but also against the human spliceosome, which is a validated drug target for the treatment of congenital diseases and cancers.

PubMed: 38898052
DOI: 10.1038/s41467-024-48697-0

実験手法

X-RAY DIFFRACTION (3.73 Å)