4V7W

Structure of the Thermus thermophilus ribosome complexed with chloramphenicol.

This is a non-PDB format compatible entry.

Summary for 4V7W

• Entry DOI: 10.2210/pdb4v7w/pdb
• Related: 3OHC 3OHD 3OHJ 3OHK 3OHY 3OHZ 3OI0 3OI1 3OI2 3OI3 3OI4 3OI5
• Descriptor: 16S rRNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (55 entities in total)
• Functional Keywords: ribosome, protein synthesis, chloramphenicol, ribosome-antibiotic complex, ribosome/antibiotic
• Biological source: Thermus thermophilus; More
• Total number of polymer chains: 102
• Total formula weight: 4267778.41

Authors

Bulkley, D.P.,Innis, C.A.,Blaha, G.,Steitz, T.A. (deposition date: 2010-08-16, release date: 2014-07-09, Last modification date: 2014-12-10)

Primary citation

Bulkley, D.,Innis, C.A.,Blaha, G.,Steitz, T.A.
Revisiting the structures of several antibiotics bound to the bacterial ribosome.
Proc.Natl.Acad.Sci.USA, 107:17158-17163, 2010

PubMed Abstract: The increasing prevalence of antibiotic-resistant pathogens reinforces the need for structures of antibiotic-ribosome complexes that are accurate enough to enable the rational design of novel ribosome-targeting therapeutics. Structures of many antibiotics in complex with both archaeal and eubacterial ribosomes have been determined, yet discrepancies between several of these models have raised the question of whether these differences arise from species-specific variations or from experimental problems. Our structure of chloramphenicol in complex with the 70S ribosome from Thermus thermophilus suggests a model for chloramphenicol bound to the large subunit of the bacterial ribosome that is radically different from the prevailing model. Further, our structures of the macrolide antibiotics erythromycin and azithromycin in complex with a bacterial ribosome are indistinguishable from those determined of complexes with the 50S subunit of Haloarcula marismortui, but differ significantly from the models that have been published for 50S subunit complexes of the eubacterium Deinococcus radiodurans. Our structure of the antibiotic telithromycin bound to the T. thermophilus ribosome reveals a lactone ring with a conformation similar to that observed in the H. marismortui and D. radiodurans complexes. However, the alkyl-aryl moiety is oriented differently in all three organisms, and the contacts observed with the T. thermophilus ribosome are consistent with biochemical studies performed on the Escherichia coli ribosome. Thus, our results support a mode of macrolide binding that is largely conserved across species, suggesting that the quality and interpretation of electron density, rather than species specificity, may be responsible for many of the discrepancies between the models.

PubMed: 20876130
DOI: 10.1073/pnas.1008685107

Experimental method

X-RAY DIFFRACTION (3 Å)