The antibiotic Furvina® targets the P-site of 30S ribosomal subunits and inhibits translation initiation displaying start codon bias

Nucleic Acids Research
Attilio FabbrettiC O Gualerzi

Abstract

Furvina®, also denominated G1 (MW 297), is a synthetic nitrovinylfuran [2-bromo-5-(2-bromo-2-nitrovinyl)-furan] antibiotic with a broad antimicrobial spectrum. An ointment (Dermofural®) containing G1 as the only active principle is currently marketed in Cuba and successfully used to treat dermatological infections. Here we describe the molecular target and mechanism of action of G1 in bacteria and demonstrate that in vivo G1 preferentially inhibits protein synthesis over RNA, DNA and cell wall synthesis. Furthermore, we demonstrate that G1 targets the small ribosomal subunit, binds at or near the P-decoding site and inhibits its function interfering with the ribosomal binding of fMet-tRNA during 30S initiation complex (IC) formation ultimately inhibiting translation. Notably, this G1 inhibition displays a bias for the nature (purine vs. pyrimidine) of the 3'-base of the codon, occurring efficiently only when the mRNA directing 30S IC formation and translation contains the canonical AUG initiation triplet or the rarely found AUA triplet, but hardly occurs when the mRNA start codon is either one of the non-canonical triplets AUU or AUC. This codon discrimination by G1 is reminiscent, though of opposite type of that displayed by I...Continue Reading

References

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Citations

Oct 2, 2015·Scientific Reports·Zhiqi GaoHengliang Wang
Apr 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Attilio FabbrettiPaola Fucini
Jun 24, 2008·Molecular Cell·Pohl MilonMarina V Rodnina
Dec 18, 2013·Nature Reviews. Microbiology·Daniel N Wilson
May 7, 2015·Memórias do Instituto Oswaldo Cruz·Sergio Sifontes-RodríguezMiguel Ángel Cabrera-Pérez
Feb 1, 2019·AMB Express·Xiaofeng JiangZhengbing Lv

Methods Mentioned

BETA
light scattering
enzyme-linked immunosorbent assay
X-ray

Related Concepts

Furvina
Antibiotics
Tetrahydrofurans
Peptide Chain Initiation, Translational
Vinyl Compounds
Codon, Initiator
Ribosome Subunits, Small, Bacterial
Codon (Nucleotide Sequence)
DNA
Physiological Aspects

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