High-resolution crystal structures of ribosome-bound chloramphenicol and erythromycin provide the ultimate basis for their competition

Svetlov, Maxim S.; Plessa, Elena; Chen, Chih-Wei; Bougas, Anthony; Krokidis, Marios G.; Dinos, George P.; Polikanov, Yury S.

doi:10.1261/rna.069260.118

High-resolution crystal structures of ribosome-bound chloramphenicol and erythromycin provide the ultimate basis for their competition

Journal Article · Thu Feb 07 00:00:00 EST 2019 · RNA

DOI:https://doi.org/10.1261/rna.069260.118· OSTI ID:1543007

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Univ. of Illinois, Chicago, IL (United States)
Univ. of Patras (Greece)

The 70S ribosome is a major target for antibacterial drugs. Two of the classical antibiotics, chloramphenicol (CHL) and erythromycin (ERY), competitively bind to adjacent but separate sites on the bacterial ribosome: the catalytic peptidyl transferase center (PTC) and the nascent polypeptide exit tunnel (NPET), respectively. The previously reported competitive binding of CHL and ERY might be due either to a direct collision of the two drugs on the ribosome or due to a drug-induced allosteric effect. Because of the resolution limitations, the available structures of these antibiotics in complex with bacterial ribosomes do not allow us to discriminate between these two possible mechanisms. In this work, we have obtained two crystal structures of CHL and ERY in complex with the Thermus thermophilus 70S ribosome at a higher resolution (2.65 and 2.89 Å, respectively) allowing unambiguous placement of the drugs in the electron density maps. Our structures provide evidence of the direct collision of CHL and ERY on the ribosome, which rationalizes the observed competition between the two drugs.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Illinois State; National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); Office of Research Infrastructure Programs (ORIP); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1543007

Journal Information:: RNA, Journal Name: RNA Journal Issue: 5 Vol. 25; ISSN 1355-8382

Publisher:: Cambridge University PressCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
70S ribosome
X-ray structure
antibiotic
chloramphenicol
competition
erythromycin
inhibition of translation
nascent peptide exit tunnel
peptidyl transferase center

High-resolution crystal structures of ribosome-bound chloramphenicol and erythromycin provide the ultimate basis for their competition

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References (38)

Cited By (3)

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