Structural characterization of an alternative mode of tigecycline binding to the bacterial ribosome

Antimicrobial Agents and Chemotherapy
Andreas SchedlbauerPaola Fucini

Abstract

Although both tetracycline and tigecycline inhibit protein synthesis by sterically hindering the binding of tRNA to the ribosomal A site, tigecycline shows increased efficacy in both in vitro and in vivo activity assays and escapes the most common resistance mechanisms associated with the tetracycline class of antibiotics. These differences in activities are attributed to the tert-butyl-glycylamido side chain found in tigecycline. Our structural analysis by X-ray crystallography shows that tigecycline binds the bacterial 30S ribosomal subunit with its tail in an extended conformation and makes extensive interactions with the 16S rRNA nucleotide C1054. These interactions restrict the mobility of C1054 and contribute to the antimicrobial activity of tigecycline, including its resistance to the ribosomal protection proteins.

Citations

Sep 23, 2016·Future Medicinal Chemistry·Samuel A McKie
May 19, 2017·FEMS Microbiology Reviews·Shiri Navon-VeneziaAlessandra Carattoli
Sep 28, 2016·Antimicrobial Agents and Chemotherapy·Fang HeYunsong Yu
Jul 25, 2019·International Journal of Molecular Sciences·Zhen DongHongjuan Cui
Jun 27, 2020·Nature Reviews. Microbiology·Daniel N WilsonAlex J O'Neill
Sep 16, 2020·Pharmacological Reviews·Ai-Ming YuMei-Juan Tu
Jun 3, 2021·International Journal of Molecular Sciences·Rya EroYong-Gui Gao
Jul 16, 2021·Frontiers in Microbiology·Victor BarrenecheaPohl Milón
May 22, 2020·ACS Infectious Diseases·Weijia LiWei Lin

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