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. 2015 Feb 27;427(4):753-755.
doi: 10.1016/j.jmb.2014.12.018. Epub 2015 Jan 3.

Bactobolin A binds to a site on the 70S ribosome distinct from previously seen antibiotics

Alexey Amunts  1 , Karol Fiedorczuk  1 , Thao T Truong  2 , Josephine Chandler  2 , E Peter Greenberg  2 , V Ramakrishnan  3
Affiliations

Bactobolin A binds to a site on the 70S ribosome distinct from previously seen antibiotics

Alexey Amunts et al. J Mol Biol. .

Abstract

The ribosome is the target of a large number of antibiotics. Here, we report a 3.4-Å-resolution crystal structure of bactobolin A bound to 70S ribosome-tRNA complex. The antibiotic binds at a previously unseen site in the 50S subunit and displaces tRNA bound at the P-site. It thus likely has a similar mechanism of action as blasticidin S despite binding to a different site. The structure also rationalizes previously identified resistance mutations.

Keywords: P-site; antibiotic; tRNA; translation.

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Figures

None
Graphical abstract
Fig. 1
Fig. 1
Binding of bactobolin A to the ribosome in the presence of P-tRNA. (a) Chemical structure of bactobolin. (b) Relative positions of bactobolin, tRNA and uL2; overlapping of bactobolin and BlaS binding sites. (c) Unbiased Fo − Fc difference map corresponding to bactobolin A and adjacent Mg2 + ion (yellow sphere) is contoured at 3σ. rRNA forming contacts with bactobolin is shown. E236 of uL2 stabilizes A2450. (d) Superposition of tRNA in the 70S-tRNA-bactobolin complex with that from antibiotic-free 70S-tRNA, demonstrating the shift of the CCA end toward the A-site.
See this image and copyright information in PMC

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