6OM7

Human ribosome nascent chain complex (PCSK9-RNC) stalled by a drug-like small molecule with AA and PE tRNAs

これはPDB形式変換不可エントリーです。

6OM7 の概要

• エントリーDOI: 10.2210/pdb6om7/pdb
• EMDBエントリー: 0526 0596 0597 0598 0599 0600 0601
• 分子名称: 18S ribosomal RNA, 40S ribosomal protein S11, 40S ribosomal protein S15, ... (87 entities in total)
• 機能のキーワード: selective stalling, drug-like small molecule, human ribosome nascent chain complex, ribosome
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 83
• 化学式量合計: 3182622.08

構造登録者

Li, W.,Cate, J.H.D. (登録日: 2019-04-18, 公開日: 2019-06-19, 最終更新日: 2025-01-29)

主引用文献

Li, W.,Ward, F.R.,McClure, K.F.,Chang, S.T.,Montabana, E.,Liras, S.,Dullea, R.G.,Cate, J.H.D.
Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule.
Nat.Struct.Mol.Biol., 26:501-509, 2019

PubMed Abstract: The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ribosome nascent chain complexes, PF846 binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S ribosomal RNA, and alters the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state of translocation, in which the peptidyl-transfer RNA 3'-CCA end is improperly docked in the peptidyl transferase center. Selections of messenger RNAs from mRNA libraries using translation extracts reveal that PF846 can stall translation elongation, arrest termination or even enhance translation, depending on nascent chain sequence context. These results illuminate how a small molecule selectively targets translation by the human ribosome, and provides a foundation for developing small molecules that modulate the production of proteins of therapeutic interest.

PubMed: 31160784
DOI: 10.1038/s41594-019-0236-8

実験手法

ELECTRON MICROSCOPY (3.7 Å)