9E5I

env2 cobalamin riboswitch aptamer domain in complex with ethynyl-4-nitrobenzene-cobalamin

これはPDB形式変換不可エントリーです。

9E5I の概要

• エントリーDOI: 10.2210/pdb9e5i/pdb
• 分子名称: RNA (76-MER), ethynyl-4-nitrobenzene-cobalamin, N-methylpropane-1,3-diamine, ... (7 entities in total)
• 機能のキーワード: riboswitch, aptamer, vitamin b12, cobalamin, rna
• 由来する生物種: marine metagenome
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53376.93

構造登録者

Olenginski, L.T.,Batey, R.T. (登録日: 2024-10-28, 公開日: 2025-09-24)

主引用文献

Olenginski, L.T.,Wierzba, A.J.,Laursen, S.P.,Batey, R.T.
Designing small molecules targeting a cryptic RNA binding site through base displacement.
Nat.Chem.Biol., 2025

PubMed Abstract: Most RNA-binding small molecules have limited solubility, weak affinity and/or lack of specificity, restricting the medicinal chemistry often required for lead compound discovery. We reasoned that conjugation of these unfavorable ligands to a suitable 'host' molecule can solubilize the 'guest' and deliver it site-specifically to an RNA of interest to resolve these issues. Using this framework, we designed a small-molecule library that was hosted by cobalamin (Cbl) to interact with the Cbl riboswitch through a common base displacement mechanism. Combining in vitro binding, cell-based assays, chemoinformatic modeling and structure-based design, we unmasked a cryptic binding site within the riboswitch that was exploited to discover compounds that have affinity exceeding the native ligand, antagonize riboswitch function or bear no resemblance to Cbl. These data demonstrate how a privileged biphenyl-like scaffold effectively targets RNA by optimizing π-stacking interactions within the binding pocket.

PubMed: 40883492
DOI: 10.1038/s41589-025-02018-8

実験手法

X-RAY DIFFRACTION (1.42 Å)