4U3U

Crystal structure of Cycloheximide bound to the yeast 80S ribosome

これはPDB形式変換不可エントリーです。

4U3U の概要

• エントリーDOI: 10.2210/pdb4u3u/pdb
• 分子名称: 18S ribosomal RNA, 40S ribosomal protein S8-A, 40S ribosomal protein S9-A, ... (89 entities in total)
• 機能のキーワード: translation, ribosome, 40s, 60s, 80s, eukaryote, rna-protein complex, inhibitor, antibiotic
• 由来する生物種: Saccharomyces cerevisiae S288c; 詳細
• タンパク質・核酸の鎖数: 162
• 化学式量合計: 6631498.96

構造登録者

Garreau de Loubresse, N.,Prokhorova, I.,Yusupova, G.,Yusupov, M. (登録日: 2014-07-22, 公開日: 2014-10-22, 最終更新日: 2024-11-06)

主引用文献

Garreau de Loubresse, N.,Prokhorova, I.,Holtkamp, W.,Rodnina, M.V.,Yusupova, G.,Yusupov, M.
Structural basis for the inhibition of the eukaryotic ribosome.
Nature, 513:517-522, 2014

PubMed Abstract: The ribosome is a molecular machine responsible for protein synthesis and a major target for small-molecule inhibitors. Compared to the wealth of structural information available on ribosome-targeting antibiotics in bacteria, our understanding of the binding mode of ribosome inhibitors in eukaryotes is currently limited. Here we used X-ray crystallography to determine 16 high-resolution structures of 80S ribosomes from Saccharomyces cerevisiae in complexes with 12 eukaryote-specific and 4 broad-spectrum inhibitors. All inhibitors were found associated with messenger RNA and transfer RNA binding sites. In combination with kinetic experiments, the structures suggest a model for the action of cycloheximide and lactimidomycin, which explains why lactimidomycin, the larger compound, specifically targets the first elongation cycle. The study defines common principles of targeting and resistance, provides insights into translation inhibitor mode of action and reveals the structural determinants responsible for species selectivity which could guide future drug development.

PubMed: 25209664
DOI: 10.1038/nature13737

実験手法

X-RAY DIFFRACTION (2.9 Å)