2PWT

Crystal structure of the bacterial ribosomal decoding site complexed with aminoglycoside containing the L-HABA group

2PWT の概要

• エントリーDOI: 10.2210/pdb2pwt/pdb
• 分子名称: 22-mer of the ribosomal decoding site, DOUBLY FUNCTIONALIZED PAROMOMYCIN PM-II-162 (3 entities in total)
• 機能のキーワード: aminoglycoside; haba group; ribosomal decoding site; x-ray analysis; rna, rna-antibiotic complex, rna/antibiotic
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16078.00

構造登録者

Kondo, J.,Pachamuthu, K.,Francois, B.,Szychowski, J.,Hanessian, S.,Westhof, E. (登録日: 2007-05-13, 公開日: 2007-09-18, 最終更新日: 2024-03-13)

主引用文献

Kondo, J.,Pachamuthu, K.,Francois, B.,Szychowski, J.,Hanessian, S.,Westhof, E.
Crystal Structure of the Bacterial Ribosomal Decoding Site Complexed with a Synthetic Doubly Functionalized Paromomycin Derivative: a New Specific Binding Mode to an A-Minor Motif Enhances in vitro Antibacterial Activity
Chemmedchem, 2:1631-1638, 2007

PubMed Abstract: The crystal structure of the complex between oligonucleotide containing the bacterial ribosomal decoding site (A site) and the synthetic paromomycin analogue 1, which contains the gamma-amino-alpha-hydroxybutyryl (L-haba) group at position N1 of ring II (2-DOS ring), and an ether chain with an O-phenethylaminoethyl group at position C2'' of ring III, is reported. Interestingly, next to the paromomycin analogue 1 specifically bound to the A site, a second molecule of 1 with a different conformation is observed at the crystal packing interface which mimics the A-minor interaction between two bulged-out adenines from the A site and the codon-anticodon stem of the mRNA-tRNA complex. Improved antibacterial activity supports the conclusion that analogue 1 might affect protein synthesis on the ribosome in two different ways: 1) specific binding to the A site forces maintenance of the "on" state with two bulged out adenines, and 2) a new binding mode of 1 to an A-minor motif which stabilizes complex formation between the ribosome and the mRNA-tRNA complex regardless of whether the codon-anticodon stem is of the cognate or near-cognate type.

PubMed: 17722211
DOI: 10.1002/cmdc.200700113

実験手法

X-RAY DIFFRACTION (1.8 Å)