4W2I

Crystal structure of the Thermus thermophilus 70S ribosome in complex with negamycin, mRNA and three deacylated tRNAs in the A, P and E sites

これはPDB形式変換不可エントリーです。

4W2I の概要

• エントリーDOI: 10.2210/pdb4w2i/pdb
• 分子名称: 16S Ribosomal RNA, 30S Ribosomal Protein S10, 30S Ribosomal Protein S11, ... (61 entities in total)
• 機能のキーワード: negamycin, antibiotic, 70s ribosome, inhibition of translation, miscoding, translocation inhibitor, 30s subunit with negamycin, mrna, deacylated a-, p-, and e-site trnas of the 1st 70s ribosome in the asu, functional complex of bacterial 70s ribosome with antibiotic negamycin, 50s subunit of the 1st 70s ribosome in the asu, ribosome-antibiotic complex, ribosome/antibiotic
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 112
• 化学式量合計: 4555287.71

構造登録者

Polikanov, Y.S.,Szal, T.,Jiang, F.,Gupta, P.,Matsuda, R.,Shiozuka, M.,Steitz, T.A.,Vazquez-Laslop, N.,Mankin, A.S. (登録日: 2014-09-12, 公開日: 2014-10-15, 最終更新日: 2023-12-27)

主引用文献

Polikanov, Y.S.,Szal, T.,Jiang, F.,Gupta, P.,Matsuda, R.,Shiozuka, M.,Steitz, T.A.,Vazquez-Laslop, N.,Mankin, A.S.
Negamycin Interferes with Decoding and Translocation by Simultaneous Interaction with rRNA and tRNA.
Mol.Cell, 56:541-550, 2014

PubMed Abstract: Negamycin (NEG) is a ribosome-targeting antibiotic that exhibits clinically promising activity. Its binding site and mode of action have remained unknown. We solved the structure of the Thermus thermophilus ribosome bound to mRNA and three tRNAs, in complex with NEG. The drug binds to both small and large ribosomal subunits at nine independent sites. Resistance mutations in the 16S rRNA unequivocally identified the binding site in the vicinity of the conserved helix 34 (h34) in the small subunit as the primary site of antibiotic action in the bacterial and, possibly, eukaryotic ribosome. At this site, NEG contacts 16S rRNA as well as the anticodon loop of the A-site tRNA. Although the NEG site of action overlaps with that of tetracycline (TET), the two antibiotics exhibit different activities: while TET sterically hinders binding of aminoacyl-tRNA to the ribosome, NEG stabilizes its binding, thereby inhibiting translocation and stimulating miscoding.

PubMed: 25306922
DOI: 10.1016/j.molcel.2014.09.021

実験手法

X-RAY DIFFRACTION (2.7 Å)