5KCR

Cryo-EM structure of the Escherichia coli 70S ribosome in complex with antibiotic Avilamycin C, mRNA and P-site tRNA at 3.6A resolution

This is a non-PDB format compatible entry.

Summary for 5KCR

• Entry DOI: 10.2210/pdb5kcr/pdb
• Related: 5KCS
• EMDB information: 8237 8238
• Descriptor: 23S Ribosomal RNA, 50S ribosomal protein L11, 50S ribosomal protein L13, ... (57 entities in total)
• Functional Keywords: avilamycin, evernimycin, antibiotic, antimicrobial, ribosome, cryo-em, smfret, rrna, l16, resistance, translation
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 55
• Total formula weight: 2196451.25

Authors

Arenz, S.,Juette, M.F.,Graf, M.,Nguyen, F.,Huter, P.,Polikanov, Y.S.,Blanchard, S.C.,Wilson, D.N. (deposition date: 2016-06-06, release date: 2016-08-17, Last modification date: 2024-10-23)

Primary citation

Arenz, S.,Juette, M.F.,Graf, M.,Nguyen, F.,Huter, P.,Polikanov, Y.S.,Blanchard, S.C.,Wilson, D.N.
Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome.
Proc.Natl.Acad.Sci.USA, 113:7527-7532, 2016

PubMed Abstract: The ribosome is one of the major targets for therapeutic antibiotics; however, the rise in multidrug resistance is a growing threat to the utility of our current arsenal. The orthosomycin antibiotics evernimicin (EVN) and avilamycin (AVI) target the ribosome and do not display cross-resistance with any other classes of antibiotics, suggesting that they bind to a unique site on the ribosome and may therefore represent an avenue for development of new antimicrobial agents. Here we present cryo-EM structures of EVN and AVI in complex with the Escherichia coli ribosome at 3.6- to 3.9-Å resolution. The structures reveal that EVN and AVI bind to a single site on the large subunit that is distinct from other known antibiotic binding sites on the ribosome. Both antibiotics adopt an extended conformation spanning the minor grooves of helices 89 and 91 of the 23S rRNA and interacting with arginine residues of ribosomal protein L16. This binding site overlaps with the elbow region of A-site bound tRNA. Consistent with this finding, single-molecule FRET (smFRET) experiments show that both antibiotics interfere with late steps in the accommodation process, wherein aminoacyl-tRNA enters the peptidyltransferase center of the large ribosomal subunit. These data provide a structural and mechanistic rationale for how these antibiotics inhibit the elongation phase of protein synthesis.

PubMed: 27330110
DOI: 10.1073/pnas.1604790113

Experimental method

ELECTRON MICROSCOPY (3.6 Å)