3jq4

The structure of the complex of the large ribosomal subunit from D. Radiodurans with the antibiotic lankacidin

spinqualitylabelsall models 3jq4, resolution 3.52Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3jq4 is a 2 chain structure with sequence from Deinococcus radiodurans R1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.52Å Ligands: LC2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Crystallographic analysis revealed that the 17-member polyketide antibiotic lankacidin produced by Streptomyces rochei binds at the peptidyl transferase center of the eubacterial large ribosomal subunit. Biochemical and functional studies verified this finding and showed interference with peptide bond formation. Chemical probing indicated that the macrolide lankamycin, a second antibiotic produced by the same species, binds at a neighboring site, at the ribosome exit tunnel. These two antibiotics can bind to the ribosome simultaneously and display synergy in inhibiting bacterial growth. The binding site of lankacidin and lankamycin partially overlap with the binding site of another pair of synergistic antibiotics, the streptogramins. Thus, at least two pairs of structurally dissimilar compounds have been selected in the course of evolution to act synergistically by targeting neighboring sites in the ribosome. These results underscore the importance of the corresponding ribosomal sites for development of clinically relevant synergistic antibiotics and demonstrate the utility of structural analysis for providing new directions for drug discovery. The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics.,Auerbach T, Mermershtain I, Davidovich C, Bashan A, Belousoff M, Wekselman I, Zimmerman E, Xiong L, Klepacki D, Arakawa K, Kinashi H, Mankin AS, Yonath A Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1983-8. Epub 2010 Jan 11. PMID:20080686 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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