4B3T

Crystal structure of the 30S ribosome in complex with compound 39

4B3T の概要

• エントリーDOI: 10.2210/pdb4b3t/pdb
• 関連するPDBエントリー: 4B3M 4B3R 4B3S
• 分子名称: 16S RIBOSOMAL RNA, 30S RIBOSOMAL PROTEIN S10, 30S RIBOSOMAL PROTEIN S11, ... (28 entities in total)
• 機能のキーワード: ribosome, aminoglycoside, antibiotic
• 由来する生物種: THERMUS THERMOPHILUS HB8; 詳細
• タンパク質・核酸の鎖数: 23
• 化学式量合計: 795777.54

構造登録者

Ng, C.L.,Lang, K.,Shcherbakov, D.,Matt, T.,Perez-Fernandez, D.,Patak, R.,Meyer, M.,Duscha, S.,Akbergenov, R.,Boukari, H.,Freihofer, P.,Kudyba, I.,Reddy, M.S.K.,Nandurikar, R.S.,Ramakrishnan, V.,Vasella, A.,Bottger, E.C. (登録日: 2012-07-26, 公開日: 2013-08-07, 最終更新日: 2024-11-20)

主引用文献

Perez-Fernandez, D.,Shcherbakov, D.,Matt, T.,Leong, N.C.,Kudyba, I.,Duscha, S.,Boukari, H.,Patak, R.,Dubakka, S.R.,Lang, K.,Meyer, M.,Akbergenov, R.,Freihofer, P.,Vaddi, S.,Thommes, P.,Ramakrishnan, V.,Vasella, A.,Bottger, E.C.
4'-O-Substitutions Determine Selectivity of Aminoglycoside Antibiotics
Nat.Commun., 5:3112-, 2014

PubMed Abstract: Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets.

PubMed: 24473108
DOI: 10.1038/NCOMMS4112

実験手法

X-RAY DIFFRACTION (3 Å)