3JQ4

The structure of the complex of the large ribosomal subunit from D. Radiodurans with the antibiotic lankacidin

3JQ4 の概要

• エントリーDOI: 10.2210/pdb3jq4/pdb
• 関連するPDBエントリー: 1NKW
• 分子名称: 23S ribosomal RNA, 5S ribosomal RNA, N-[(1S,2R,3E,5E,7S,9E,11E,13S,15R,19R)-7,13-dihydroxy-1,4,10,19-tetramethyl-17,18-dioxo-16-oxabicyclo[13.2.2]nonadeca-3,5,9,11-tetraen-2-yl]-2-oxopropanamide (3 entities in total)
• 機能のキーワード: ribosome structure, antibiotics, lankacidin, lankamycin, protein synthesis, inhibitors, synergism, macrolide, rna
• 由来する生物種: Deinococcus radiodurans; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 971894.31

構造登録者

Auerbach-Nevo, T.,Mermershtain, I.,Davidovich, C.,Bashan, A.,Rozenberg, H.,Yonath, A. (登録日: 2009-09-06, 公開日: 2010-09-08, 最終更新日: 2023-11-01)

主引用文献

Auerbach, T.,Mermershtain, I.,Davidovich, C.,Bashan, A.,Belousoff, M.,Wekselman, I.,Zimmerman, E.,Xiong, L.,Klepacki, D.,Arakawa, K.,Kinashi, H.,Mankin, A.S.,Yonath, A.
The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics
Proc.Natl.Acad.Sci.USA, 107:1983-1988, 2010

PubMed Abstract: Crystallographic analysis revealed that the 17-member polyketide antibiotic lankacidin produced by Streptomyces rochei binds at the peptidyl transferase center of the eubacterial large ribosomal subunit. Biochemical and functional studies verified this finding and showed interference with peptide bond formation. Chemical probing indicated that the macrolide lankamycin, a second antibiotic produced by the same species, binds at a neighboring site, at the ribosome exit tunnel. These two antibiotics can bind to the ribosome simultaneously and display synergy in inhibiting bacterial growth. The binding site of lankacidin and lankamycin partially overlap with the binding site of another pair of synergistic antibiotics, the streptogramins. Thus, at least two pairs of structurally dissimilar compounds have been selected in the course of evolution to act synergistically by targeting neighboring sites in the ribosome. These results underscore the importance of the corresponding ribosomal sites for development of clinically relevant synergistic antibiotics and demonstrate the utility of structural analysis for providing new directions for drug discovery.

PubMed: 20080686
DOI: 10.1073/pnas.0914100107

実験手法

X-RAY DIFFRACTION (3.52 Å)