5kcr | pdb_00005kcr
Cryo-EM structure of the Escherichia coli 70S ribosome in complex with antibiotic Avilamycin C, mRNA and P-site tRNA at 3.6A resolution
Structural highlights
FunctionRL2_ECOLI One of the primary rRNA binding proteins. Located near the base of the L1 stalk, it is probably also mobile. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is highly controversial.[HAMAP-Rule:MF_01320_B] In the E.coli 70S ribosome in the initiation state it has been modeled to make several contacts with the 16S rRNA (forming bridge B7b, PubMed:12809609); these contacts are broken in the model with bound EF-G.[HAMAP-Rule:MF_01320_B] Publication Abstract from PubMedThe 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-A 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. Structures of the orthosomycin antibiotics avilamycin and evernimicin in complex with the bacterial 70S ribosome.,Arenz S, Juette MF, Graf M, Nguyen F, Huter P, Polikanov YS, Blanchard SC, Wilson DN Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7527-32. doi:, 10.1073/pnas.1604790113. Epub 2016 Jun 21. PMID:27330110[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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